# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 5803 | 0 | 0.9974 | Face mask sampling reveals antimicrobial resistance genes in exhaled aerosols from patients with chronic obstructive pulmonary disease and healthy volunteers. INTRODUCTION: The degree to which bacteria in the human respiratory tract are aerosolised by individuals is not established. Building on our experience sampling bacteria exhaled by individuals with pulmonary tuberculosis using face masks, we hypothesised that patients with conditions frequently treated with antimicrobials, such as chronic obstructive pulmonary disease (COPD), might exhale significant numbers of bacteria carrying antimicrobial resistance (AMR) genes and that this may constitute a previously undefined risk for the transmission of AMR. METHODS: Fifteen-minute mask samples were taken from 13 patients with COPD (five paired with contemporaneous sputum samples) and 10 healthy controls. DNA was extracted from cell pellets derived from gelatine filters mounted within the mask. Quantitative PCR analyses directed to the AMR encoding genes: blaTEM (β-lactamase), ErmB (target methylation), mefA (macrolide efflux pump) and tetM (tetracycline ribosomal protection protein) and six additional targets were investigated. Positive signals above control samples were obtained for all the listed genes; however, background signals from the gelatine precluded analysis of the additional targets. RESULTS: 9 patients with COPD (69%), aerosolised cells containing, in order of prevalence, mefA, tetM, ErmB and blaTEM, while three healthy controls (30%) gave weak positive signals including all targets except blaTEM. Maximum estimated copy numbers of AMR genes aerosolised per minute were mefA: 3010, tetM: 486, ErmB: 92 and blaTEM: 24. The profile of positive signals found in sputum was not concordant with that in aerosol in multiple instances. DISCUSSION: We identified aerosolised AMR genes in patients repeatedly exposed to antimicrobials and in healthy volunteers at lower frequencies and levels. The discrepancies between paired samples add weight to the view that sputum content does not define aerosol content. Mask sampling is a simple approach yielding samples from all subjects and information distinct from sputum analysis. Our results raise the possibility that patient-generated aerosols may be a significant means of AMR dissemination that should be assessed further and that consideration be given to related control measures. | 2018 | 30271606 |
| 4617 | 1 | 0.9969 | A maximum likelihood QTL analysis reveals common genome regions controlling resistance to Salmonella colonization and carrier-state. BACKGROUND: The serovars Enteritidis and Typhimurium of the Gram-negative bacterium Salmonella enterica are significant causes of human food poisoning. Fowl carrying these bacteria often show no clinical disease, with detection only established post-mortem. Increased resistance to the carrier state in commercial poultry could be a way to improve food safety by reducing the spread of these bacteria in poultry flocks. Previous studies identified QTLs for both resistance to carrier state and resistance to Salmonella colonization in the same White Leghorn inbred lines. Until now, none of the QTLs identified was common to the two types of resistance. All these analyses were performed using the F2 inbred or backcross option of the QTLExpress software based on linear regression. In the present study, QTL analysis was achieved using Maximum Likelihood with QTLMap software, in order to test the effect of the QTL analysis method on QTL detection. We analyzed the same phenotypic and genotypic data as those used in previous studies, which were collected on 378 animals genotyped with 480 genome-wide SNP markers. To enrich these data, we added eleven SNP markers located within QTLs controlling resistance to colonization and we looked for potential candidate genes co-localizing with QTLs. RESULTS: In our case the QTL analysis method had an important impact on QTL detection. We were able to identify new genomic regions controlling resistance to carrier-state, in particular by testing the existence of two segregating QTLs. But some of the previously identified QTLs were not confirmed. Interestingly, two QTLs were detected on chromosomes 2 and 3, close to the locations of the major QTLs controlling resistance to colonization and to candidate genes involved in the immune response identified in other, independent studies. CONCLUSIONS: Due to the lack of stability of the QTLs detected, we suggest that interesting regions for further studies are those that were identified in several independent studies, which is the case of the QTL regions on chromosomes 2 and 3, involved in resistance to both Salmonella colonization and carrier state. These observations provide evidence of common genes controlling S. Typhimurium colonization and S. Enteritidis carrier-state in chickens. | 2012 | 22613937 |
| 465 | 2 | 0.9969 | Diversity of ionizing radiation-resistant bacteria obtained from the Taklimakan Desert. So far, little is known about the diversity of the radiation-resistant microbes of the hyperarid Taklimakan Desert. In this study, ionizing radiation (IR)-resistant bacteria from two sites in Xinjiang were investigated. After exposing the arid (water content of 0.8 ± 0.3%) and non-arid (water content of 21.3 ± 0.9%) sediment samples to IR of 3000 Gy using a (60)Co source, a total of 52 γ-radiation-resistant bacteria were isolated from the desert sample. The 16S rRNA genes of all isolates were sequenced. The phylogenetic tree places these isolates into five groups: Cytophaga-Flavobacterium-Bacteroides, Proteobacteria, Deinococcus-Thermus, Firmicutes, and Actinobacteria. Interestingly, this is the first report of radiation-resistant bacteria belonging to the genera Knoellia, Lysobacter, Nocardioides, Paracoccus, Pontibacter, Rufibacter and Microvirga. The 16s rRNA genes of four isolates showed low sequence similarities to those of the published species. Phenotypic analysis showed that all bacteria in this study are able to produce catalase, suggesting that these bacteria possess reactive oxygen species (ROS)-scavenging enzymes. These radiation-resistant bacteria also displayed diverse metabolic properties. Moreover, their radiation resistances were found to differ. The diversity of the radiation-resistant bacteria in the desert provides further ecological support for the hypothesis that the ionizing-radiation resistance phenotype is a consequence of the evolution of ROS-scavenging systems that protect cells against oxidative damage caused by desiccation. | 2015 | 25590873 |
| 6032 | 3 | 0.9969 | Toxigenic potential and heat survival of spore-forming bacteria isolated from bread and ingredients. Fifty-four spore-forming bacterial strains isolated from bread ingredients and bread, mainly belonging to the genus Bacillus (including Bacillus cereus), together with 11 reference strains were investigated to evaluate their cytotoxic potential and heat survival in order to ascertain if they could represent a risk for consumer health. Therefore, we performed a screening test of cytotoxic activity on HT-29 cells using bacterial culture filtrates after growing bacterial cells in Brain Heart Infusion medium and in the bread-based medium Bread Extract Broth (BEB). Moreover, immunoassays and PCR analyses, specifically targeting already known toxins and related genes of B. cereus, as well as a heat spore inactivation assay were carried out. Despite of strain variability, the results clearly demonstrated a high cytotoxic activity of B. cereus strains, even if for most of them it was significantly lower in BEB medium. Cytotoxic activity was also detected in 30% of strains belonging to species different from B. cereus, although, with a few exceptions (e.g. Bacillus simplex N58.2), it was low or very low. PCR analyses detected the presence of genes involved in the production of NHE, HBL or CytK toxins in B. cereus strains, while genes responsible for cereulide production were not detected. Production of NHE and HBL toxins was also confirmed by specific immunoassays only for B. cereus strains even if PCR analyses revealed the presence of related toxin genes also in some strains of other species. Viable spore count was ascertained after a heat treatment simulating the bread cooking process. Results indicated that B. amyloliquefaciens strains almost completely survived the heat treatment showing less than 2 log-cycle reductions similarly to two strains of B. cereus group III and single strains belonging to Bacillus subtilis, Bacillus mojavensis and Paenibacillus spp. Importantly, spores from strains of the B. cereus group IV exhibited a thermal resistance markedly lower than B. cereus group III with high values of log-cycle reductions. In conclusion, our results indicate that spore-forming bacteria contaminating bread ingredients and bread could represent a source of concern for consumer health related to the presence of strains, such as strains of B. cereus group III and single strains of other species, showing the ability to produce toxic substances associated to a thermal resistance enough to survive the bread cooking conditions. | 2015 | 25555227 |
| 8445 | 4 | 0.9969 | A genome-wide association study in catfish reveals the presence of functional hubs of related genes within QTLs for columnaris disease resistance. BACKGROUND: Columnaris causes severe mortalities among many different wild and cultured freshwater fish species, but understanding of host resistance is lacking. Catfish, the primary aquaculture species in the United States, serves as a great model for the analysis of host resistance against columnaris disease. Channel catfish in general is highly resistant to the disease while blue catfish is highly susceptible. F2 generation of hybrids can be produced where phenotypes and genotypes are segregating, providing a useful system for QTL analysis. To identify genes associated with columnaris resistance, we performed a genome-wide association study (GWAS) using the catfish 250 K SNP array with 340 backcross progenies derived from crossing female channel catfish (Ictalurus punctatus) with male F1 hybrid catfish (female channel catfish I. punctatus × male blue catfish I. furcatus). RESULTS: A genomic region on linkage group 7 was found to be significantly associated with columnaris resistance. Within this region, five have known functions in immunity, including pik3r3b, cyld-like, adcyap1r1, adcyap1r1-like, and mast2. In addition, 3 additional suggestively associated QTL regions were identified on linkage groups 7, 12, and 14. The resistant genotypes on the QTLs of linkage groups 7 and 12 were found to be homozygous with both alleles being derived from channel catfish. The paralogs of the candidate genes in the suggestively associated QTL of linkage group 12 were found on the QTLs of linkage group 7. Many candidate genes on the four associated regions are involved in PI3K pathway that is known to be required by many bacteria for efficient entry into the host. CONCLUSION: The GWAS revealed four QTLs associated with columnaris resistance in catfish. Strikingly, the candidate genes may be arranged as functional hubs; the candidate genes within the associated QTLs on linkage groups 7 and 12 are not only co-localized, but also functionally related, with many of them being involved in the PI3K signal transduction pathway, suggesting its importance for columnaris resistance. | 2015 | 25888203 |
| 8843 | 5 | 0.9968 | Dual RNA-seq in Streptococcus pneumoniae Infection Reveals Compartmentalized Neutrophil Responses in Lung and Pleural Space. Streptococcus pneumoniae is the dominant cause of community-acquired pneumonia worldwide. Invasion of the pleural space is common and results in increased mortality. We set out to determine the bacterial and host factors that influence invasion of the pleural space. In a murine model of pneumococcal infection, we isolated neutrophil-dominated samples of bronchoalveolar and pleural fluid containing bacteria 48 hours after infection. Using dual RNA sequencing (RNA-seq), we characterized bacterial and host transcripts that were differentially regulated between these compartments and bacteria in broth and resting neutrophils, respectively. Pleural and lung samples showed upregulation of genes involved in the positive regulation of neutrophil extravasation but downregulation of genes mediating bacterial killing. Compared to the lung samples, cells within the pleural space showed marked upregulation of many genes induced by type I interferons, which are cytokines implicated in preventing bacterial transmigration across epithelial barriers. Differences in the bacterial transcripts between the infected samples and bacteria grown in broth showed the upregulation of genes in the bacteriocin locus, the pneumococcal surface adhesin PsaA, and the glycopeptide resistance gene vanZ; the gene encoding the ClpP protease was downregulated in infection. One hundred sixty-nine intergenic putative small bacterial RNAs were also identified, of which 43 (25.4%) small RNAs had been previously described. Forty-two of the small RNAs were upregulated in pleura compared to broth, including many previously identified as being important in virulence. Our results have identified key host and bacterial responses to invasion of the pleural space that can be potentially exploited to develop alternative antimicrobial strategies for the prevention and treatment of pneumococcal pleural disease.IMPORTANCE The factors that regulate the passage of bacteria between different anatomical compartments are unclear. We have used an experimental model of infection with Streptococcus pneumoniae to examine the host and bacterial factors involved in the passage of bacteria from the lung to the pleural space. The transcriptional profile of host and bacterial cells within the pleural space and lung was analyzed using deep sequencing of the entire transcriptome using the technique of dual RNA-seq. We found significant differences in the host and bacterial RNA profiles in infection, which shed light on the key factors that allow passage of this bacterium into the pleural space. | 2019 | 31409659 |
| 2543 | 6 | 0.9968 | Capturing the antibiotic resistome of preterm infants reveals new benefits of probiotic supplementation. BACKGROUND: Probiotic use in preterm infants can mitigate the impact of antibiotic exposure and reduce rates of certain illnesses; however, the benefit on the gut resistome, the collection of antibiotic resistance genes, requires further investigation. We hypothesized that probiotic supplementation of early preterm infants (born < 32-week gestation) while in hospital reduces the prevalence of antibiotic resistance genes associated with pathogenic bacteria in the gut. We used a targeted capture approach to compare the resistome from stool samples collected at the term corrected age of 40 weeks for two groups of preterm infants (those that routinely received a multi-strain probiotic during hospitalization and those that did not) with samples from full-term infants at 10 days of age to identify if preterm birth or probiotic supplementation impacted the resistome. We also compared the two groups of preterm infants up to 5 months of age to identify persistent antibiotic resistance genes. RESULTS: At the term corrected age, or 10 days of age for the full-term infants, we found over 80 antibiotic resistance genes in the preterm infants that did not receive probiotics that were not identified in either the full-term or probiotic-supplemented preterm infants. More genes associated with antibiotic inactivation mechanisms were identified in preterm infants unexposed to probiotics at this collection time-point compared to the other infants. We further linked these genes to mobile genetic elements and Enterobacteriaceae, which were also abundant in their gut microbiomes. Various genes associated with aminoglycoside and beta-lactam resistance, commonly found in pathogenic bacteria, were retained for up to 5 months in the preterm infants that did not receive probiotics. CONCLUSIONS: This pilot survey of preterm infants shows that probiotics administered after preterm birth during hospitalization reduced the diversity and prevented persistence of antibiotic resistance genes in the gut microbiome. The benefits of probiotic use on the microbiome and the resistome should be further explored in larger groups of infants. Due to its high sensitivity and lower sequencing cost, our targeted capture approach can facilitate these surveys to further address the implications of resistance genes persisting into infancy without the need for large-scale metagenomic sequencing. Video Abstract. | 2022 | 36008821 |
| 6235 | 7 | 0.9967 | EHEC/EAEC O104:H4 strain linked with the 2011 German outbreak of haemolytic uremic syndrome enters into the viable but non-culturable state in response to various stresses and resuscitates upon stress relief. Various non-spore forming bacteria, including Escherichia coli, enter a dormant-like state, the viable but non-culturable (VBNC) state, characterized by the presence of viable cells but the inability to grow on routine laboratory media. Upon resuscitation, these VBNC cells recover both culturability and pathogenicity. In 2011, a large outbreak involving more than 3000 cases of bloody diarrhoea and haemolytic uremic syndrome was caused by an E. coli O104:H4 strain expressing genes characteristic of both enterohaemorrhagic (EHEC) and enteroaggregative E. coli (EAEC). The ability of the outbreak strain to enter the VBNC state may have complicated its detection in the suspected sources. In this paper, we investigated the ability of the outbreak strain to enter and subsequently recover from the VBNC state. We found that in a nutrient-poor micro-environment, various stresses such as toxic concentrations of copper ions or certain types of tap water are able to render the bacteria unculturable within a few days. Without copper ion stress, the majority of cells remained culturable for at least 40 days. Incubation with the stressors at 23°C compared with 4°C hastened this observed loss of culturability. The integrity of a considerable fraction of copper ion- and tap water 1-stressed bacteria was demonstrated by live/dead staining and microscopy. Relieving stress by copper-ion chelation facilitated resuscitation of these bacteria while preserving their fitness, major virulence gene markers (stx2, aggR, aggA genes) and specific phenotypes (ESBL resistance, autoaggregation typical for EAEC strains). | 2011 | 21951606 |
| 5742 | 8 | 0.9967 | Associations between antimicrobial resistance phenotypes, antimicrobial resistance genes, and virulence genes of fecal Escherichia coli isolates from healthy grow-finish pigs. Escherichia coli often carries linked antimicrobial resistance genes on transmissible genetic elements. Through coselection, antimicrobial use may select for unrelated but linked resistance or virulence genes. This study used unconditional statistical associations to investigate the relationships between antimicrobial resistance phenotypes and antimicrobial resistance genes in 151 E. coli isolates from healthy pigs. Phenotypic resistance to each drug was significantly associated with phenotypic resistance to at least one other drug, and every association found that the probability of observing the outcome resistance was increased by the presence of the predictor resistance. With one exception, each statistical association that was identified between a pair of resistance genes had a corresponding significant association identified between the phenotypes mediated by those genes. This suggests that associations between resistance phenotypes might predict coselection. If this hypothesis is confirmed, evaluation of the associations between resistance phenotypes could improve our knowledge of coselection dynamics and provide a cost-effective way to evaluate existing data until large-scale genotypic data collection becomes feasible. This could enable policy makers and users of antimicrobials to consider coselection in antimicrobial use decisions. This study also considered the unconditional relationships between resistance and virulence genes in E. coli from healthy pigs (aidA-1, eae, elt, estA, estB, fedA1, stx1, and stx2). Positive statistical associations would suggest that antimicrobial use may select for virulence in bacteria that may contaminate food or cause diarrhea in pigs. Fortunately, the odds of detecting a virulence gene were rarely increased by the presence of an antimicrobial resistance gene. This suggests that on-farm antimicrobial use did not select for the examined virulence factors in E. coli carried by this population of healthy pigs. | 2009 | 19139228 |
| 4739 | 9 | 0.9967 | Indirect resistance to several classes of antibiotics in cocultures with resistant bacteria expressing antibiotic-modifying or -degrading enzymes. OBJECTIVES: Indirect resistance (IR), the ability of an antibiotic-resistant population of bacteria to protect a susceptible population, has been previously observed for β-lactamase-producing bacteria and associated with antimicrobial treatment failures. Here, we determined whether other resistance determinants could cause IR in the presence of five other classes of antibiotics. METHODS: A test was designed to detect IR and 14 antibiotic resistance genes were tested in the presence of 13 antibiotics from six classes. A bioassay was used to measure the ability of resistance-causing enzymes to decrease the concentration of active antibiotics in the medium. RESULTS: We confirmed IR in the presence of β-lactam antibiotics (ampicillin and mecillinam) when TEM-1A was expressed. We found that bacteria expressing antibiotic-modifying or -degrading enzymes Ere(A), Tet(X2) or CatA1 caused IR in the presence of macrolides (erythromycin and clarithromycin), tetracyclines (tetracycline and tigecycline) and chloramphenicol, respectively. IR was not observed with resistance determinants that did not modify or destroy antibiotics or with enzymes modifying aminoglycosides or degrading fosfomycin. IR was dependent on the resistance enzymes decreasing the concentration of active antibiotics in the medium, hence allowing nearby susceptible bacteria to resume growth once the antibiotic concentration fell below their MIC. CONCLUSIONS: IR was not limited to β-lactamase-producing bacteria, but was also caused by resistant bacteria carrying cytoplasmic antibiotic-modifying or -degrading enzymes that catalyse energy-consuming reactions requiring complex cellular cofactors. Our results suggest that IR is common and further emphasizes that coinfecting agents and the human microflora can have a negative impact during antimicrobial therapy. | 2016 | 26467993 |
| 2555 | 10 | 0.9966 | Results of the antimicrobial agent susceptibility study raised in a representative, cross-sectional monitoring study on a national basis. The use of antimicrobial substances in human and veterinary medicine inevitably results in a selection pressure for drug resistance in exposed bacteria. Preventive measures, apt to avoid the consequent development of new resistances and selection for existing ones, respectively, have to be elaborated. Moreover, it has to be ensured that neither resistant bacteria nor resistance genes are spread to and consequently via the food chain. Respiratory diseases as well as mastitis in dairy cattle belong to the most frequently occurring diseases in food-producing animals. For the first time in Germany, a comprehensive, cross-sectional study into the antimicrobial susceptibility of bacteria associated with these disease patterns in food-producing animals was conducted by the Federal Office of Consumer Protection and Food Safety (BVL) in 2001. The selection of examined bacterial species comprised Pasteurella multocida and Mannheimia haemolytica associated with respiratory disease in pigs, and Escherichia coli, Streptococcus spp. and Staphylococcus spp. causing mastitis in dairy cattle. Bacterial strains were collected following a representative sampling scheme, taking into account the total number of animals in the individual German federal Länder. In an analogous study conducted in 2002/2003, this selection was extended by the indication respiratory disease in juvenile cattle, caused by P. multocida and M. haemolytica, respectively. In comparison with data from 2001, MIC values determined in 2002/2003 suggested significantly lower or higher degrees of drug susceptibility only for a few antimicrobial agents. Comparison was carried out on the basis of bacterial species and individual federal Länder, respectively. Overall, the data raised in both studies revealed substantially lower resistance rates than published for Germany so far. This is particularly true for results from those Länder, whose animal health services had implemented preventive strategies to control infectious diseases. No correlation could be established between differing animal population densities and differences in the prevalence of resistance in corresponding Lander. However, the geographical distribution of occurrence of resistance against beta-lactam antimicrobial agents suggests different therapeutic strategies employed in different sized animal flocks. In federal Länder marked by large-scale livestock farming, significantly higher resistance values could be measured for cephalosporins than for penicillins, whereas in Länder with rather traditional farming structures, resistance to penicillins was predominant. Assuming otherwise similar factors of influence on the emergence of resistance, this pattern suggests that cephalosporins are preferably used in large enterprises and penicillins in smaller farms, respectively. Currently, mechanisms effecting changes in antimicrobial resistance are being further investigated in a successive study. | 2006 | 16531116 |
| 5702 | 11 | 0.9966 | Disinfectant Susceptibility of Third-Generation-Cephalosporin/Carbapenem-Resistant Gram-Negative Bacteria Isolated from the Oral Cavity of Residents of Long-Term-Care Facilities. We have recently reported the isolation of third-generation-cephalosporin-resistant Gram-negative bacteria from the oral cavity of residents of a long-term-care facility (LTCF). Since disinfectants are often used in the oral cavity, it is important to investigate the disinfectant susceptibility of oral bacteria. Here, we evaluated the susceptibilities of Gram-negative antimicrobial-resistant bacteria (GN-ARB), including Pseudomonas, Acinetobacter, and Enterobacteriaceae, obtained from the oral cavity of residents of LTCFs to povidone-iodine (PVPI), cetylpyridinium chloride (CPC), benzalkonium chloride (BZK), and chlorhexidine chloride (CHX). We also evaluated the susceptibilities of isolates from the rectum to the same agents to compare the susceptibility profiles of oral and rectal isolates. Next, we investigated the relationship between their susceptibility and disinfectant resistance genes delineated by whole-genome sequencing of the isolates. Additionally, we evaluated the correlation between disinfectant-resistant GN-ARB and clinical information. In oral GN-ARB, the MIC of PVPI showed almost identical values across isolates, while the MICs of CPC, BZK, and CHX showed a wide range of variation among species/strains. In particular, Pseudomonas aeruginosa exhibited high-level resistance to CPC and BZK. The disinfectant susceptibility of rectal GN-ARB showed a tendency similar to that of oral GN-ARB. The presence of qacEΔ1 was correlated with CPC/BZK resistance in P. aeruginosa, while other species exhibited no correlation between qacEΔ1 and resistance. Multiple analyses showed the correlation between the presence of CPC-resistant bacteria in the oral cavity and tube feeding. In conclusion, we found that some oral GN-ARB isolates showed resistance to not only antibiotics but also disinfectants. IMPORTANCE Antibiotic-resistant bacteria (ARB) are becoming a serious concern worldwide. We previously reported the isolation of third-generation-cephalosporin-resistant Gram-negative bacteria from the oral cavity of residents of a long-term-care facility (LTCF). To prevent infection with ARB in hospitals and eldercare facilities, we must pay more attention to the use of not only antibiotics but also disinfectants. However, the effect of disinfectants on ARB is unclear. In this study, we evaluated the susceptibility of Gram-negative ARB (GN-ARB) from the oral cavity of residents of LTCFs to some disinfectants that are often used for the oral cavity; we found that some isolates showed resistance to several disinfectants. This is the first comprehensive analysis of the disinfectant susceptibility of oral GN-ARB. These results provide some important information for infection control and suggest that disinfectants should be applied carefully. | 2023 | 36515531 |
| 5669 | 12 | 0.9966 | Screening and Potential of the Incidence of Resistance Transfer Among the Multidrug and Heavy Metal Resistant Gram-Negative Isolates from Hospital Effluents of Northern India. BACKGROUND: Hospital wastewater has a high amount of both organic and inorganic matter, as well as high densities of living organisms, including pathogenic, and environmental bacteria. It has been suggested that genes encoding resistance to an antibiotic can be located together with heavy metals resistance genes on either the same genetic structure (plasmid) or different genetic structures within the same bacterial strain. Resistance transfer is mainly attributed to conjugation since many antimicrobial resistance genes are situated on mobile elements, such as plasmids and conjugative transposons, whereas renovation and transduction are usually more limited. Our study confirmed the flow of resistance genes between indigenous and foreign organisms and indicated the possibility of resistance transfer from environmental reservoirs to pathogenic strains, which should be underlined in the future. The recent patents on drug resistance (US20030130169, WO/2001/060387, WO/2016/151092) and gene transfer (JP2003189855, JP2010094090), helped in this study. METHODS: Water samples were collected from three different sites of hospital wastewater. Isolation of Gram-negative bacteria from hospital wastewater samples was done using the standard microbial procedure. The heavy metal resistance was determined by the minimum inhibitory concentration (MIC) against the test bacterial strain by spot plate method. The antibiotic resistance was determined by a standard disc diffusion technique. The bacterial resistance transfer studies were determined between donor and recipient strain in nutrient as well as wastewater. The antibiogram and MIC of the donors and transconjugants were studied by above-described methods. RESULTS: A high number of Gram-Negative Bacterial Isolates (GNB) exhibited antibiotic and metal resistance transfer into E. coli K-12 and similar GNB isolates in nutrient broth as compared to wastewater. The microbial conjugation experiments showed that a high percentage of multi-resistant GNB (75% and 66%) was able to transfer their single or multidrug resistance patterns to E. coli K-12 among antibiotic while 58%, 66% of the multiresistant isolates were able to transfer their single or multi-metal resistance patterns to E. coli K-12 among metal in nutrient medium and wastewater, respectively. In the present conjugation study, 97.5% and 70% of the total tested GNB isolates were able to transfer an antibiotic-resistant marker to recipient GNB in both the medium (nutrient medium and wastewater), whereas 92.5% and72.5% of the isolates were able to transfer metal resistant marker to recipient GNB in nutrient medium and wastewater from all the site tested. The higher (6.8x10-1 and 5.9x10-1) frequency of transfer was observed among antibiotic and metal while the lower frequency of transfer was (7.0x10-3 and 2.0x10-3) exhibited against antibiotic and metal in both the medium from the entire site tested, respectively. CONCLUSION: We can recommend that the hospital water is heavily polluted with several types of antibiotics, toxic metals as well as the potentially hazardous bacterial flora because of their capacity to resist one or the other well known antibiotic and chemotherapeutic agents. These studies provide evidence that a wide variety of clinically important antibiotic and metal resistance genes is mobile within aquatic bacterial communities one step ahead of the above, we can envisage the alarming situation prevailing in our system and surrounding in the light of transmissible nature of R-plasmids. | 2018 | 29984669 |
| 5667 | 13 | 0.9966 | Quantifying antibiotic impact on within-patient dynamics of extended-spectrum beta-lactamase resistance. Antibiotic-induced perturbation of the human gut flora is expected to play an important role in mediating the relationship between antibiotic use and the population prevalence of antibiotic resistance in bacteria, but little is known about how antibiotics affect within-host resistance dynamics. Here we develop a data-driven model of the within-host dynamics of extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae. We use bla(CTX-M) (the most widespread ESBL gene family) and 16S rRNA (a proxy for bacterial load) abundance data from 833 rectal swabs from 133 ESBL-positive patients followed up in a prospective cohort study in three European hospitals. We find that cefuroxime and ceftriaxone are associated with increased bla(CTX-M) abundance during treatment (21% and 10% daily increase, respectively), while treatment with meropenem, piperacillin-tazobactam, and oral ciprofloxacin is associated with decreased bla(CTX-M) (8% daily decrease for all). The model predicts that typical antibiotic exposures can have substantial long-term effects on bla(CTX-M) carriage duration. | 2020 | 32379042 |
| 4910 | 14 | 0.9966 | Excreted Antibiotics May Be Key to Emergence of Increasingly Efficient Antibiotic Resistance in Food Animal Production. At a time when antibiotic resistance is seemingly ubiquitous worldwide, understanding the mechanisms responsible for successful emergence of new resistance genes may provide insights into the persistence and pathways of dissemination for antibiotic-resistant organisms in general. For example, Escherichia coli strains harboring a class A β-lactamase-encoding gene (bla(CTX-M-15)) appear to be displacing strains that harbor a class C β-lactamase gene (bla(CMY-2)) in Washington State dairy cattle. We cloned these genes with native promoters into low-copy-number plasmids that were then transformed into isogenic strains of E. coli, and growth curves were generated for two commonly administered antibiotics (ampicillin and ceftiofur). Both strains met the definition of resistance for ampicillin (≥32 μg/mL) and ceftiofur (≥16 μg/mL). Growth of the CMY-2-producing strain was compromised at 1,000 μg/mL ampicillin, whereas the CTX-M-15-producing strain was not inhibited in the presence of 3,000 μg/mL ampicillin or with most concentrations of ceftiofur, although there were mixed outcomes with ceftiofur metabolites. Consequently, in the absence of competing genes, E. coli harboring either gene would experience a selective advantage if exposed to these antibiotics. Successful emergence of CTX-M-15-producing strains where CMY-2-producing strains are already established, however, requires high concentrations of antibiotics that can only be found in the urine of treated animals (e.g., >2,000 μg/mL for ampicillin, based on literature). This ex vivo selection pressure may be important for the emergence of new and more efficient antibiotic resistance genes and likely for persistence of antibiotic-resistant bacteria in food animal populations. IMPORTANCE We studied the relative fitness benefits of a cephalosporin resistance enzyme (CTX-M-15) that is displacing a similar enzyme (CMY-2), which is extant in E. coli from dairy cattle in Washington State. In vitro experiments demonstrated that CTX-M-15 provides a significant fitness advantage, but only in the presence of very high concentrations of antibiotic that are only found when the antibiotic ampicillin, and to a lesser extent ceftiofur, is excreted in urine from treated animals. As such, the increasing prevalence of bacteria with bla(CTX-M-15) is likely occurring ex vivo. Interventions should focus on controlling waste from treated animals and, when possible, selecting antibiotics that are less likely to impact the proximal environment of treated animals. | 2022 | 35867586 |
| 6290 | 15 | 0.9966 | Transcriptomic profiling of ceftriaxone-tolerant phenotypes of Neisseria gonorrhoeae reveals downregulation of ribosomal genes - a pilot study. Antibiotic tolerance is associated with failure of antibiotic treatment and accelerates the development of antimicrobial resistance. The molecular mechanisms underlying antimicrobial tolerance remain poorly understood. Tolerant bacteria can slow metabolism by extending the lag phase without altering antimicrobial susceptibility. We recently induced ceftriaxone (CRO) tolerance in the Neisseria gonorrhoeae reference strain WHO P. In the current study, we characterized the transcriptomic profiles of these CRO-tolerant phenotypes. To induce tolerance, WHO P strains were grown under 3-h intermittent CRO exposure (10× the MIC), followed by overnight growth in gonococcal (GC) broth for seven consecutive days, with cultures maintained in sextuplicate. Two control cultures were maintained without CRO exposure. The tolerance and CRO susceptibility of the isolates were assessed using a modified tolerance disc (TD) test. Total RNA was isolated from tolerant isolates (n = 12) and control (n = 3) strains, followed by Ribo depletion, Illumina Library preparation, and sequencing. Transcriptomic analysis revealed no differentially expressed genes after 1 day of CRO exposure. However, after 3 days of CRO exposure, 13 genes were found to be significantly downregulated, including tRNA-Ser (C7S06_RS03100) and tRNA-Leu (C7S06_RS04945) and ribosomal RNA genes (16S and 23S rRNA). Following 7 days of exposure, 51 genes were differentially expressed, with most downregulated, such as SecB (Protein-export chaperone SecB) and tRNA-Ser (C7S06_RS01850) and the 16S and 23S ribosomal RNA genes. The development of CRO-tolerance in N. gonorrhoeae was associated with the downregulation of various ribosomal genes and associated genes, reflecting a potential mechanism for bacterial survival under antibiotic stress. IMPORTANCE: Antibiotic tolerance allows some bacteria to survive antibiotic treatment, contributing to treatment failure and creating conditions that promote resistance. In this study, we showed that Neisseria gonorrhoeae, the bacteria that causes gonorrhea, can become tolerant to ceftriaxone-the last-line treatment used. By repeatedly exposing the bacteria to high doses of ceftriaxone, we observed the development of tolerance over several days. Using transcriptomic analysis, we found that tolerant bacteria consistently reduced the activity of genes involved in protein synthesis, including ribosomal RNAs and transfer RNAs. This suggests that N. gonorrhoeae may survive antibiotic stress by entering a low-metabolic state that makes the antibiotic less effective. These findings highlight a survival mechanism that does not rely on genetic resistance. Understanding this tolerance response is vital for improving current treatment approaches and could inform the development of new strategies to prevent antibiotic failure in gonorrhea and other infections. | 2025 | 40622217 |
| 5168 | 16 | 0.9966 | Bacteriophage Resistance Affects Flavobacterium columnare Virulence Partly via Mutations in Genes Related to Gliding Motility and the Type IX Secretion System. Increasing problems with antibiotic resistance have directed interest toward phage therapy in the aquaculture industry. However, phage resistance evolving in target bacteria is considered a challenge. To investigate how phage resistance influences the fish pathogen Flavobacterium columnare, two wild-type bacterial isolates, FCO-F2 and FCO-F9, were exposed to phages (FCO-F2 to FCOV-F2, FCOV-F5, and FCOV-F25, and FCO-F9 to FCL-2, FCOV-F13, and FCOV-F45), and resulting phenotypic and genetic changes in bacteria were analyzed. Bacterial viability first decreased in the exposure cultures but started to increase after 1 to 2 days, along with a change in colony morphology from original rhizoid to rough, leading to 98% prevalence of the rough morphotype. Twenty-four isolates (including four isolates from no-phage treatments) were further characterized for phage resistance, antibiotic susceptibility, motility, adhesion, and biofilm formation, protease activity, whole-genome sequencing, and virulence in rainbow trout fry. The rough isolates arising in phage exposure were phage resistant with low virulence, whereas rhizoid isolates maintained phage susceptibility and high virulence. Gliding motility and protease activity were also related to the phage susceptibility. Observed mutations in phage-resistant isolates were mostly located in genes encoding the type IX secretion system, a component of the Bacteroidetes gliding motility machinery. However, not all phage-resistant isolates had mutations, indicating that phage resistance in F. columnare is a multifactorial process, including both genetic mutations and changes in gene expression. Phage resistance may not, however, be a challenge for development of phage therapy against F. columnare infections since phage resistance is associated with decreases in bacterial virulence. IMPORTANCE Phage resistance of infectious bacteria is a common phenomenon posing challenges for the development of phage therapy. Along with a growing world population and the need for increased food production, constantly intensifying animal farming has to face increasing problems of infectious diseases. Columnaris disease, caused by Flavobacterium columnare, is a worldwide threat for salmonid fry and juvenile farming. Without antibiotic treatments, infections can lead to 100% mortality in a fish stock. Phage therapy of columnaris disease would reduce the development of antibiotic-resistant bacteria and antibiotic loads by the aquaculture industry, but phage-resistant bacterial isolates may become a risk. However, phenotypic and genetic characterization of phage-resistant F. columnare isolates in this study revealed that they are less virulent than phage-susceptible isolates and thus not a challenge for phage therapy against columnaris disease. This is valuable information for the fish farming industry globally when considering phage-based prevention and curing methods for F. columnare infections. | 2021 | 34106011 |
| 4813 | 17 | 0.9966 | Evaluating the Effectiveness of Hospital Antiseptics on Multidrug-Resistant Acinetobacter baumannii: Understanding the Relationship between Microbicide and Antibiotic Resistance. Acinetobacter baumannii hospital infections are difficult to treat due to the rapid emergence of multidrug-resistant (MDR) strains. In addition, A. baumannii can survive in numerous adverse environments, including in the presence of common hospital antiseptics. We hypothesized that in addition to accumulating drug resistance determinants, MDR A. baumannii strains also accumulate mutations that allow for greater microbicide tolerance when compared to pan-susceptible (PS) strains. To test this hypothesis, we compared the survival of five MDR and five PS patient isolates when exposed to bleach, ethanol, quaternary ammonium compounds, chlorhexidine gluconate, and povidone. We evaluated bacteria in a free-living planktonic state and under biofilm conditions. Each disinfectant eliminated 99.9% of planktonic bacteria, but this was not the case for bacterial biofilms. Next, we characterized strains for the presence of the known microbicide-resistance genes cepA, qacEΔ1, qacE, and qacA. MDR strains did not survive more than PS strains in the presence of microbicides, but microbicide-resistant strains had higher survival rates under some conditions. Interestingly, the PS strains were more likely to possess microbicide-resistance genes. Microbicide resistance remains an important topic in healthcare and may be independent of antimicrobial resistance. Hospitals should consider stricter isolation precautions that take pan-susceptible strains into account. | 2022 | 35625258 |
| 6272 | 18 | 0.9966 | Inactivation of ackA and pta Genes Reduces GlpT Expression and Susceptibility to Fosfomycin in Escherichia coli. Fosfomycin is used to treat a variety of bacterial infections, including urinary tract infections caused by Escherichia coli. In recent years, quinolone-resistant and extended-spectrum β-lactamase (ESBL)-producing bacteria have been increasing. Because fosfomycin is effective against many of these drug-resistant bacteria, the clinical importance of fosfomycin is increasing. Against this background, information on the mechanisms of resistance and the antimicrobial activity of this drug is desired to enhance the usefulness of fosfomycin therapy. In this study, we aimed to explore novel factors affecting the antimicrobial activity of fosfomycin. Here, we found that ackA and pta contribute to fosfomycin activity against E. coli. ackA and pta mutant E. coli had reduced fosfomycin uptake capacity and became less sensitive to this drug. In addition, ackA and pta mutants had decreased expression of glpT that encodes one of the fosfomycin transporters. Expression of glpT is enhanced by a nucleoid-associated protein, Fis. We found that mutations in ackA and pta also caused a decrease in fis expression. Thus, we interpret the decrease in glpT expression in ackA and pta defective strains to be due to a decrease in Fis levels in these mutants. Furthermore, ackA and pta are conserved in multidrug-resistant E. coli isolated from patients with pyelonephritis and enterohemorrhagic E. coli, and deletion of ackA and pta from these strains resulted in decreased susceptibility to fosfomycin. These results suggest that ackA and pta in E. coli contribute to fosfomycin activity and that mutation of these genes may pose a risk of reducing the effect of fosfomycin. IMPORTANCE The spread of drug-resistant bacteria is a major threat in the field of medicine. Although fosfomycin is an old type of antimicrobial agent, it has recently come back into the limelight because of its effectiveness against many drug-resistant bacteria, including quinolone-resistant and ESBL-producing bacteria. Since fosfomycin is taken up into the bacteria by GlpT and UhpT transporters, its antimicrobial activity fluctuates with changes in GlpT and UhpT function and expression. In this study, we found that inactivation of the ackA and pta genes responsible for the acetic acid metabolism system reduced GlpT expression and fosfomycin activity. In other words, this study shows a new genetic mutation that leads to fosfomycin resistance in bacteria. The results of this study will lead to further understanding of the mechanism of fosfomycin resistance and the creation of new ideas to enhance fosfomycin therapy. | 2023 | 37199605 |
| 8944 | 19 | 0.9966 | Polyphosphate Kinase Mediates Antibiotic Tolerance in Extraintestinal Pathogenic Escherichia coli PCN033. Extraintestinal pathogenic Escherichia coli (ExPEC) causes a variety of acute infections in its hosts, and multidrug-resistant strains present significant challenges to public health and animal husbandry. Therefore, it is necessary to explore new drug targets to control E. coli epidemics. Previous studies have reported that ppk mutants of Burkholderia pseudomallei and Mycobacterium tuberculosis are more susceptible than the wild types (WTs) to stress. Therefore, we investigated the stress response to antibiotics mediated by polyphosphate kinase (PPK) in ExPEC strain PCN033. We observed that planktonic cells of a ppk knockout strain (Δppk) were more susceptible to antibiotics than was WT. However, biofilm-grown Δppk cells showed similar susceptibility to that of the WT and were more tolerant than the planktonic cells. During the planktonic lifestyle, the expression of genes involved in antibiotic tolerance (including resistance-conferring genes, and antibiotic influx, and efflux genes) did not change in the Δppk mutant without antibiotic treatment. However, the resistance-conferring gene bla and efflux genes were upregulated more in the WT than in the Δppk mutant by treatment with tazobactam. After treatment with gentamycin, the efflux genes and influx genes were upregulated and downregulated, respectively, more in the WT than in the Δppk mutant. The expression of genes involved in biofilm regulation also changed after treatment with tazobactam or gentamycin, and which is consistent with the results of the biofilm formation. Together, these observations indicate that PPK is important for the antibiotic stress response during the planktonic growth of ExPEC and might be a potential drug target in bacteria. | 2016 | 27242742 |