Resistome analysis of bloodstream infection bacterial genomes reveals a specific set of proteins involved in antibiotic resistance and drug efflux. - Related Documents




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462501.0000Resistome analysis of bloodstream infection bacterial genomes reveals a specific set of proteins involved in antibiotic resistance and drug efflux. Bacterial resistance to antibiotics is a global public health problem. Its association with bloodstream infections is even more severe and may easily evolve to sepsis. To improve our response to these bacteria, it is essential to gather thorough knowledge on the main pathogens along with the main mechanisms of resistance they carry. In this paper, we performed a large meta-analysis of 3872 bacterial genomes isolated from blood samples, from which we identified 71 745 antibiotic resistance genes (ARGs). Taxonomic analysis showed that Proteobacteria and Firmicutes phyla, and the species Klebsiella pneumoniae and Staphylococcus aureus were the most represented. Comparison of ARGs with the Resfams database showed that the main mechanism of antibiotic resistance is mediated by efflux pumps. Clustering analysis between resistome of blood and soil-isolated bacteria showed that there is low identity between transport and efflux proteins between bacteria from these environments. Furthermore, a correlation analysis among all features showed that K. pneumoniae and S. aureus formed two well-defined clusters related to the resistance mechanisms, proteins and antibiotics. A retrospective analysis has shown that the average number of ARGs per genome has gradually increased. The results demonstrate the importance of comprehensive studies to understand the antibiotic resistance phenomenon.202033575606
432010.9999The mobilome landscape of biocide-resistance in Brazilian ESKAPE isolates. The increasing frequency of antibiotic-resistant bacteria is a constant threat to global human health. Therefore, the pathogens of the ESKAPE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, and Enterobacter spp.) are among the most relevant causes of hospital infections responsible for millions of deaths every year. However, little has been explored about the danger of microorganisms resistant to biocides such as antiseptics and disinfectants. Widely used in domestic, industrial, and hospital environments, these substances reach the environment and can cause selective pressure for resistance genes and induce cross-resistance to antibiotics, further aggravating the problem. Therefore, it is necessary to use innovative and efficient strategies to monitor the spread of genes related to resistance to biocides. Whole genome sequencing and bioinformatics analysis aiming to search for sequences encoding resistance mechanisms are essential to help monitor and combat these pathogens. Thus, this work describes the construction of a bioinformatics tool that integrates different databases to identify gene sequences that may confer some resistance advantage about biocides. Furthermore, the tool analyzed all the genomes of Brazilian ESKAPE isolates deposited at NCBI and found a series of different genes related to resistance to benzalkonium chloride, chlorhexidine, and triclosan, which were the focus of this work. As a result, the presence of resistance genes was identified in different types of biological samples, environments, and hosts. Regarding mobile genetic elements (MGEs), around 52% of isolates containing genes related to resistance to these compounds had their genes identified in plasmids, and 48.7% in prophages. These data show that resistance to biocides can be a silent, underestimated danger spreading across different environments and, therefore, requires greater attention.202439028534
462620.9999Prophages Present in Acinetobacter pittii Influence Bacterial Virulence, Antibiotic Resistance, and Genomic Rearrangements. Introduction: Antibiotic resistance and virulence are common among bacterial populations, posing a global clinical challenge. The bacterial species Acinetobacter pittii, an infectious agent in clinical environments, has shown increasing rates of antibiotic resistance. Viruses that integrate as prophages into A. pittii could be a potential cause of this pathogenicity, as they often contain antibiotic resistance or virulence factor gene sequences. Methods: In this study, we analyzed 25 A. pittii strains for potential prophages. Using virulence factor databases, we identified many common and virulent prophages in A. pittii. Results: The analysis also included a specific catalogue of the virulence factors and antibiotic resistance genes contributed by A. pittii prophages. Finally, our results illustrate multiple similarities between A. pittii and its bacterial relatives with regard to prophage integration sites and prevalence. Discussion: These findings provide a broader insight into prophage behavior that can be applied to future studies on similar species in the Acinetobacter calcoaceticus-baumannii complex.202236161193
438030.9999Comparative genome analysis of ciprofloxacin-resistant Pseudomonas aeruginosa reveals genes within newly identified high variability regions associated with drug resistance development. The alarming rise of ciprofloxacin-resistant Pseudomonas aeruginosa has been reported in several clinical studies. Though the mutation of resistance genes and their role in drug resistance has been researched, the process by which the bacterium acquires high-level resistance is still not well understood. How does the genomic evolution of P. aeruginosa affect resistance development? Could the exposure of antibiotics to the bacteria enrich genomic variants that lead to the development of resistance, and if so, how are these variants distributed through the genome? To answer these questions, we performed 454 pyrosequencing and a whole genome analysis both before and after exposure to ciprofloxacin. The comparative sequence data revealed 93 unique resistance strain variation sites, which included a mutation in the DNA gyrase subunit A gene. We generated variation-distribution maps comparing the wild and resistant types, and isolated 19 candidates from three discrete resistance-associated high variability regions that had available transposon mutants, to perform a ciprofloxacin exposure assay. Of these region candidates with transposon disruptions, 79% (15/19) showed a reduction in the ability to gain high-level resistance, suggesting that genes within these high variability regions might enrich for certain functions associated with resistance development.201323808957
472740.9998Biodegradation of plastics and pesticides by soil bacteria in Bangladesh: Insights into antibiotic resistance and potential therapeutic targets. Soil bacteria exhibit varying degrees of tolerance to different concentrations of pesticides and plastics, and some possess the ability to degrade them, which is crucial for bioremediation. However, the multidrug-resistant properties of these bacteria pose challenges for their potential applications. Hence, this study aims to separate and characterize plastics and pesticide-degrading bacteria fromnon-contaminated and contaminated sites in Bangladesh and evaluate their antibiotic-resistant patterns to identify safety issues and discover promising therapeutic targets for combating multidrug-resistant infections. In the current study, a total of 90 soil samples were collected from different agricultural and dumped sites of Bangladesh, and bacterial isolates were screened for pesticides and plastics-degrading capabilities. Antibiotic sensitivity patterns of the potential isolates were evaluated using 16 different antibiotics. Biochemical, molecular, and genomic analyses were conducted to characterize the bacteria and identify antimicrobial resistance (AMR) genes. Our study screened out 122 plastic and 60 pesticide-tolerant bacterial isolates. Among them, 3 pesticide and 3 plastic-degrading isolates were found to be more promising and identified as Acinetobacter baumannii with pesticide-degrading capabilities from non-contaminated sites, and Klebsiella pneumoniae with plastic-degrading capabilities from contaminated sites. Antibiotic sensitivity test exhibited that most of the isolates were resistance to commonly used antimicrobials. The genomics and proteomics analysis uncovered the efflux pump-related genes responsible for the resistant mechanism and highlighted the involvement of genes that respond to antibiotics and transmembrane transport activities. Phylogenetic analysis confirmed the conservation of 2 common resistance genes adeF and gyrA, across diverse multidrug-resistant pathogens. Therefore, targeting conserved genes adeF and gyrA, to disrupt resistance mechanisms and combat persistent and clinically significant multidrug-resistant pathogens could be a promising strategy for developing combination therapies in medical science.202540854651
462950.9998Screening and in silico characterization of prophages in Helicobacter pylori clinical strains. The increase of antibiotic resistance calls for alternatives to control Helicobacter pylori, a Gram-negative bacterium associated with various gastric diseases. Bacteriophages (phages) can be highly effective in the treatment of pathogenic bacteria. Here, we developed a method to identify prophages in H. pylori genomes aiming at their future use in therapy. A polymerase chain reaction (PCR)-based technique tested five primer pairs on 74 clinical H. pylori strains. After the PCR screening, 14 strains most likely to carry prophages were fully sequenced. After that, a more holistic approach was taken by studying the complete genome of the strains. This study allowed us to identify 12 intact prophage sequences, which were then characterized concerning their morphology, virulence, and antibiotic-resistance genes. To understand the variability of prophages, a phylogenetic analysis using the sequences of all H. pylori phages reported to date was performed. Overall, we increased the efficiency of identifying complete prophages to 54.1 %. Genes with homology to potential virulence factors were identified in some new prophages. Phylogenetic analysis revealed a close relationship among H. pylori-phages, although there are phages with different geographical origins. This study provides a deeper understanding of H. pylori-phages, providing valuable insights into their potential use in therapy.202539368610
385260.9998Phenotype profiles and adaptive preference of Acinetobacter johnsonii isolated from Ba River with different environmental backgrounds. Acinetobacter johnsonii is a potentially opportunistic pathogen widely distributed in nosocomial and natural environments, but little attention has been paid to this bacillus. Here A. johnsonii strains from Ba River with different pollution levels were isolated. In this study, we found that the increasing anthropogenic contaminants accounted for the emergence of multidrug-resistant (MDR) A. johnsonii strains. Correlation analysis results showed that the resistance phenotype of strains could be generated by co-selection of heavy metals or non-corresponding antibiotics. The whole genome sequence analysis showed that the relative heavy pollution of water selects strains containing more survival-relevant genes. We found that only some genes like bla(OXA-24) were responsible for its corresponding resistance profile. Additionally, the tolerance profiles toward heavy metals also attribute to the expression of efflux pumps rather than corresponding resistance genes. In summary, our finding revealed that the resistance profiles of A. johnsonii could be generated by cross or co-selection of anthropogenic contaminants and mediated by efflux pumps instead of corresponding resistance determinants. Our study also has deep-sight into the adaptive preference of bacteria in natural environments, and contributes to surveillance studies and MDR- A. johnsonii monitoring worldwide.202133639142
464070.9998Genome analysis of probiotic bacteria for antibiotic resistance genes. To date, probiotic bacteria are used in the diet and have various clinical applications. There are reports of antibiotic resistance genes in these bacteria that can transfer to other commensal and pathogenic bacteria. The aim of this study was to use whole-genome sequence analysis to identify antibiotic resistance genes in a group of bacterial with probiotic properties. Also, this study followed existing issues about the importance and presence of antibiotic resistance genes in these bacteria and the dangers that may affect human health in the future. In the current study, a collection of 126 complete probiotic bacterial genomes was analyzed for antibiotic resistance genes. The results of the current study showed that there are various resistance genes in these bacteria that some of them are transferable to other bacteria. The tet(W) tetracycline resistance gene was more than other antibiotic resistance genes in these bacteria and this gene was found in Bifidobacterium and Lactobacillus. In our study, the most numbers of antibiotic resistance genes were transferred with mobile genetic elements. We propose that probiotic companies before the use of a micro-organism as a probiotic, perform an antibiotic susceptibility testing for a large number of antibiotics. Also, they perform analysis of complete genome sequence for prediction of antibiotic resistance genes.202234989942
462780.9998Antibiotic resistance mechanisms of Myroides sp. Bacteria of the genus Myroides (Myroides spp.) are rare opportunistic pathogens. Myroides sp. infections have been reported mainly in China. Myroides sp. is highly resistant to most available antibiotics, but the resistance mechanisms are not fully elucidated. Current strain identification methods based on biochemical traits are unable to identify strains accurately at the species level. While 16S ribosomal RNA (rRNA) gene sequencing can accurately achieve this, it fails to give information on the status and mechanisms of antibiotic resistance, because the 16S rRNA sequence contains no information on resistance genes, resistance islands or enzymes. We hypothesized that obtaining the whole genome sequence of Myroides sp., using next generation sequencing methods, would help to clarify the mechanisms of pathogenesis and antibiotic resistance, and guide antibiotic selection to treat Myroides sp. infections. As Myroides sp. can survive in hospitals and the environment, there is a risk of nosocomial infections and pandemics. For better management of Myroides sp. infections, it is imperative to apply next generation sequencing technologies to clarify the antibiotic resistance mechanisms in these bacteria.201626984839
992290.9998De novo acquisition of antibiotic resistance in six species of bacteria. Bacteria can become resistant to antibiotics in two ways: by acquiring resistance genes through horizontal gene transfer and by de novo development of resistance upon exposure to non-lethal concentrations. The importance of the second process, de novo build-up, has not been investigated systematically over a range of species and may be underestimated as a result. To investigate the DNA mutation patterns accompanying the de novo antibiotic resistance acquisition process, six bacterial species encountered in the food chain were exposed to step-wise increasing sublethal concentrations of six antibiotics to develop high levels of resistance. Phenotypic and mutational landscapes were constructed based on whole-genome sequencing at two time points of the evolutionary trajectory. In this study, we found that (1) all of the six strains can develop high levels of resistance against most antibiotics; (2) increased resistance is accompanied by different mutations for each bacterium-antibiotic combination; (3) the number of mutations varies widely, with Y. enterocolitica having by far the most; (4) in the case of fluoroquinolone resistance, a mutational pattern of gyrA combined with parC is conserved in five of six species; and (5) mutations in genes coding for efflux pumps are widely encountered in gram-negative species. The overall conclusion is that very similar phenotypic outcomes are instigated by very different genetic changes. The outcome of this study may assist policymakers when formulating practical strategies to prevent development of antimicrobial resistance in human and veterinary health care.IMPORTANCEMost studies on de novo development of antimicrobial resistance have been performed on Escherichia coli. To examine whether the conclusions of this research can be applied to more bacterial species, six species of veterinary importance were made resistant to six antibiotics, each of a different class. The rapid build-up of resistance observed in all six species upon exposure to non-lethal concentrations of antimicrobials indicates a similar ability to adjust to the presence of antibiotics. The large differences in the number of DNA mutations accompanying de novo resistance suggest that the mechanisms and pathways involved may differ. Hence, very similar phenotypes can be the result of various genotypes. The implications of the outcome are to be considered by policymakers in the area of veterinary and human healthcare.202539907470
4663100.9998Pan-genomics of Ochrobactrum species from clinical and environmental origins reveals distinct populations and possible links. Ochrobactrum genus is comprised of soil-dwelling Gram-negative bacteria mainly reported for bioremediation of toxic compounds. Since last few years, mainly two species of this genus, O. intermedium and O. anthropi were documented for causing infections mostly in the immunocompromised patients. Despite such ubiquitous presence, study of adaptation in various niches is still lacking. Thus, to gain insights into the niche adaptation strategies, pan-genome analysis was carried out by comparing 67 genome sequences belonging to Ochrobactrum species. Pan-genome analysis revealed it is an open pan-genome indicative of the continuously evolving nature of the genus. The presence/absence of gene clusters also illustrated the unique presence of antibiotic efflux transporter genes and type IV secretion system genes in the clinical strains while the genes of solvent resistance and exporter pumps in the environmental strains. A phylogenomic investigation based on 75 core genes depicted better and robust phylogenetic resolution and topology than the 16S rRNA gene. To support the pan-genome analysis, individual genomes were also investigated for the mobile genetic elements (MGE), antibiotic resistance genes (ARG), metal resistance genes (MRG) and virulence factors (VF). The analysis revealed the presence of MGE, ARG, and MRG in all the strains which play an important role in the species evolution which is in agreement with the pan-genome analysis. The average nucleotide identity (ANI) based on the genetic relatedness between the Ochrobactrum species indicated a distinction between individual species. Interestingly, the ANI tool was able to classify the Ochrobactrum genomes to the species level which were assigned till the genus level on the NCBI database.202032428556
4641110.9998Genomic insights into antibiotic resistance and mobilome of lactic acid bacteria and bifidobacteria. Lactic acid bacteria (LAB) and Bifidobacterium sp. (bifidobacteria) can carry antimicrobial resistance genes (ARGs), yet data on resistance mechanisms in these bacteria are limited. The aim of our study was to identify the underlying genetic mechanisms of phenotypic resistance in 103 LAB and bifidobacteria using whole-genome sequencing. Sequencing data not only confirmed the presence of 36 acquired ARGs in genomes of 18 strains, but also revealed wide dissemination of intrinsic ARGs. The presence of acquired ARGs on known and novel mobile genetic elements raises the possibility of their horizontal spread. In addition, our data suggest that mutations may be a common mechanism of resistance. Several novel candidate resistance mechanisms were uncovered, providing a basis for further in vitro studies. Overall, 1,314 minimum inhibitory concentrations matched with genotypes in 92.4% of the cases; however, prediction of phenotype based on genotypic data was only partially efficient, especially with respect to aminoglycosides and chloramphenicol. Our study sheds light on resistance mechanisms and their transferability potential in LAB and bifidobacteria, which will be useful for risk assessment analysis.202336781180
4631120.9998Genome Analysis of an Enterococcal Prophage, Entfac.MY. BACKGROUND: Bacteriophages are bacterial parasites. Unlike lytic bacteriophages, lysogenic bacteriophages do not multiply immediately after entering the host cells and may integrate their genomes into the bacterial genomes as prophages. Prophages can include various phenotypic and genotypic effects on the host bacteria. Enterococcus spp. are Gram-positive bacteria that cause infections in humans and animals. In recent decades, these bacteria have become resistant to various antimicrobials, including vancomycin. The aim of this study was to analyze genome of an enterococcal prophage. METHODS: In this study, Enterococcus faecium EntfacYE was isolated from biological samples and its genome was analyzed using next-generation sequencing method. RESULTS: Overall, 254 prophage genes were identified in the bacterial genome. The prophage included 39 housekeeping, 41 replication and regulation, 80 structural and packaging, and 48 lysis genes. Moreover, 46 genes with unknown functions were identified. All genes were annotated in DNA Data Bank of Japan. CONCLUSION: In general, most prophage genes were linked to packaging and structure (31.5%) gene group. However, genes with unknown functions included a high proportion (18.11%), which indicated necessity of further analyses. Genomic analysis of the prophages can be effective in better understanding of their roles in development of bacterial resistance to antibiotics. Moreover, identification and study of prophages can help researchers develop genetic engineering tools and novel infection therapies.202236061127
4728130.9998Antibiotic Resistance Profile, Outer Membrane Proteins, Virulence Factors and Genome Sequence Analysis Reveal Clinical Isolates of Enterobacter Are Potential Pathogens Compared to Environmental Isolates. Outer membrane proteins (OMPs) of gram-negative bacteria play an important role in mediating antibacterial resistance, bacterial virulence and thus affect pathogenic ability of the bacteria. Over the years, prevalence of environmental antibiotic resistant organisms, their transmission to clinics and ability to transfer resistance genes, have been studied extensively. Nevertheless, how successful environmental bacteria can be in establishing as pathogenic bacteria under clinical setting, is less addressed. In the present study, we utilized an integrated approach of investigating the antibiotic resistance profile, presence of outer membrane proteins and virulence factors to understand extent of threat posed due to multidrug resistant environmental Enterobacter isolates. Also, we investigated clinical Enterobacter isolates and compared the results thereof. Results of the study showed that multidrug resistant environmental Enterobacter isolates lacked OmpC, lacked cell invasion abilities and exhibited low reactive oxygen species (ROS) production in neutrophils. In contrast, clinical isolates possessed OmpF, exhibited high invasive and adhesive property and produced higher amounts of ROS in neutrophils. These attributes indicated limited pathogenic potential of environmental Enterobacter isolates. Informations obtained from whole genome sequence of two representative bacterial isolates from environment (DL4.3) and clinical sources (EspIMS6) corroborated well with the observed results. Findings of the present study are significant as it highlights limited fitness of multidrug resistant environmental Enterobacter isolates.202032154188
4664140.9998Comprehensive screening of genomic and metagenomic data reveals a large diversity of tetracycline resistance genes. Tetracyclines are broad-spectrum antibiotics used to prevent or treat a variety of bacterial infections. Resistance is often mediated through mobile resistance genes, which encode one of the three main mechanisms: active efflux, ribosomal target protection or enzymatic degradation. In the last few decades, a large number of new tetracycline-resistance genes have been discovered in clinical settings. These genes are hypothesized to originate from environmental and commensal bacteria, but the diversity of tetracycline-resistance determinants that have not yet been mobilized into pathogens is unknown. In this study, we aimed to characterize the potential tetracycline resistome by screening genomic and metagenomic data for novel resistance genes. By using probabilistic models, we predicted 1254 unique putative tetracycline resistance genes, representing 195 gene families (<70 % amino acid sequence identity), whereof 164 families had not been described previously. Out of 17 predicted genes selected for experimental verification, 7 induced a resistance phenotype in an Escherichia coli host. Several of the predicted genes were located on mobile genetic elements or in regions that indicated mobility, suggesting that they easily can be shared between bacteria. Furthermore, phylogenetic analysis indicated several events of horizontal gene transfer between bacterial phyla. Our results also suggested that acquired efflux pumps originate from proteobacterial species, while ribosomal protection genes have been mobilized from Firmicutes and Actinobacteria. This study significantly expands the knowledge of known and putatively novel tetracycline resistance genes, their mobility and evolutionary history. The study also provides insights into the unknown resistome and genes that may be encountered in clinical settings in the future.202033125315
4654150.9998Early Bacterial Colonization and Antibiotic Resistance Gene Acquisition in Newborns. Several studies have recently identified the main factors contributing to the bacterial colonization of newborns and the dynamics of the infant microbiome development. However, most of these studies address large time periods of weeks or months after birth, thereby missing on important aspects of the early microbiome maturation, such as the acquisition of antibiotic resistance determinants during postpartum hospitalization. The pioneer bacterial colonization and the extent of its associated antibiotic resistance gene (ARG) dissemination during this early phase of life are largely unknown. Studies addressing resistant bacteria or ARGs in neonates often focus only on the presence of particular bacteria or genes from a specific group of antibiotics. In the present study, we investigated the gut-, the oral-, and the skin-microbiota of neonates within the first 72 h after birth using 16S rDNA sequencing approaches. In addition, we screened the neonates and their mothers for the presence of 20 different ARGs by directed TaqMan qPCR assays. The taxonomic analysis of the newborn samples revealed an important shift of the microbiota during the first 72 h after birth, showing a clear site-specific colonization pattern in this very early time frame. Moreover, we report a substantial acquisition of ARGs during postpartum hospitalization, with a very high incidence of macrolide resistance determinants and mecA detection across different body sites of the newborns. This study highlights the importance of antibiotic resistance determinant dissemination in neonates during hospitalization, and the need to investigate the implication of the mothers and the hospital environment as potential sources of ARGs.202032754449
4628160.9998Genomic Analysis of Molecular Bacterial Mechanisms of Resistance to Phage Infection. To optimize phage therapy, we need to understand how bacteria evolve against phage attacks. One of the main problems of phage therapy is the appearance of bacterial resistance variants. The use of genomics to track antimicrobial resistance is increasingly developed and used in clinical laboratories. For that reason, it is important to consider, in an emerging future with phage therapy, to detect and avoid phage-resistant strains that can be overcome by the analysis of metadata provided by whole-genome sequencing. Here, we identified genes associated with phage resistance in 18 Acinetobacter baumannii clinical strains belonging to the ST-2 clonal complex during a decade (Ab2000 vs. 2010): 9 from 2000 to 9 from 2010. The presence of genes putatively associated with phage resistance was detected. Genes detected were associated with an abortive infection system, restriction-modification system, genes predicted to be associated with defense systems but with unknown function, and CRISPR-Cas system. Between 118 and 171 genes were found in the 18 clinical strains. On average, 26% of these genes were detected inside genomic islands in the 2000 strains and 32% in the 2010 strains. Furthermore, 38 potential CRISPR arrays in 17 of 18 of the strains were found, as well as 705 proteins associated with CRISPR-Cas systems. A moderately higher presence of these genes in the strains of 2010 in comparison with those of 2000 was found, especially those related to the restriction-modification system and CRISPR-Cas system. The presence of these genes in genomic islands at a higher rate in the strains of 2010 compared with those of 2000 was also detected. Whole-genome sequencing and bioinformatics could be powerful tools to avoid drawbacks when a personalized therapy is applied. In this study, it allows us to take care of the phage resistance in A. baumannii clinical strains to prevent a failure in possible phage therapy.202135250902
6279170.9998Comparative transcriptomics analyses of the different growth states of multidrug-resistant Acinetobacter baumannii. Multidrug-resistant (MDR) Acinetobacter baumannii is an important bacterial pathogen commonly associated with hospital acquired infections. A. baumannii can remain viable and hence virulent in the environment for a long period of time due primarily to its ability to form biofilms. A total of 459 cases of MDR A. baumannii our hospital collected from March 2014 to March 2015 were examined in this study, and a representative isolate selected for high-throughput mRNA sequencing and comparison of gene expression profiles under the biofilm and exponential growth conditions. Our study found that the same bacteria indeed exhibited differential mRNA expression under different conditions. Compared to the rapidly growing bacteria, biofilm bacteria had 106 genes upregulated and 92 genes downregulated. Bioinformatics analyses suggested that many of these genes are involved in the formation and maintenance of biofilms, whose expression also depends on the environment and specific signaling pathways and transcription factors that are absent in the log phase bacteria. These differentially expressed mRNAs might contribute to A. baumannii's unique pathogenicity and ability to inflict chronic and recurrent infections.201727916419
3912180.9998Genomic Sequence Analysis of Methicillin- and Carbapenem-Resistant Bacteria Isolated from Raw Sewage. Antibiotic resistance is one of the largest threats facing global health. Wastewater treatment plants are well-known hot spots for interaction between diverse bacteria, genetic exchange, and antibiotic resistance. Nonpathogenic bacteria theoretically act as reservoirs of antibiotic resistance subsequently transferring antibiotic resistance genes to pathogens, indicating that evolutionary processes occur outside clinical settings and may drive patterns of drug-resistant infections. We isolated and sequenced 100 bacterial strains from five wastewater treatment plants to analyze regional dynamics of antibiotic resistance in the California Central Valley. The results demonstrate the presence of a wide diversity of pathogenic and nonpathogenic bacteria, with an arithmetic mean of 5.1 resistance genes per isolate. Forty-three percent of resistance genes were located on plasmids, suggesting that large levels of gene transfer between bacteria that otherwise may not co-occur are facilitated by wastewater treatment. One of the strains detected was a Bacillus carrying pX01 and pX02 anthrax-like plasmids and multiple drug resistance genes. A correlation between resistance genes and taxonomy indicates that taxon-specific evolutionary studies may be useful in determining and predicting patterns of antibiotic resistance. Conversely, a lack of geographic correlation may indicate that landscape genetic studies to understand the spread of antibiotic resistance genes should be carried out at broader scales. This large data set provides insights into how pathogenic and nonpathogenic bacteria interact in wastewater environments and the resistance genes which may be horizontally transferred between them. This can help in determining the mechanisms leading to the increasing prevalence of drug-resistant infections observed in clinical settings. IMPORTANCE The reasons for the increasing prevalence of antibiotic-resistant infections are complex and associated with myriad clinical and environmental processes. Wastewater treatment plants operate as nexuses of bacterial interaction and are known hot spots for genetic exchange between bacteria, including antibiotic resistance genes. We isolated and sequenced 100 drug-resistant bacteria from five wastewater treatment plants in California's Central Valley, characterizing widespread gene sharing between pathogens and nonpathogens. We identified a novel, multiresistant Bacillus carrying anthrax-like plasmids. This empirical study supports the likelihood of evolutionary and population processes in the broader environment affecting the prevalence of clinical drug-resistant infections and identifies several taxa that may operate as reservoirs and vectors of antibiotic resistance genes.202134132566
4322190.9998Multi-Drug Resistance in Bacterial Genomes-A Comprehensive Bioinformatic Analysis. Antimicrobial resistance is presently one of the greatest threats to public health. The excessive and indiscriminate use of antibiotics imposes a continuous selective pressure that triggers the emergence of multi-drug resistance. We performed a large-scale analysis of closed bacterial genomes to identify multi-drug resistance considering the ResFinder antimicrobial classes. We found that more than 95% of the genomes harbor genes associated with resistance to disinfectants, glycopeptides, macrolides, and tetracyclines. On average, each genome encodes resistance to more than nine different classes of antimicrobial drugs. We found higher-than-expected co-occurrences of resistance genes in both plasmids and chromosomes for several classes of antibiotic resistance, including classes categorized as critical according to the World Health Organization (WHO). As a result of antibiotic-resistant priority pathogens, higher-than-expected co-occurrences appear in plasmids, increasing the potential for resistance dissemination. For the first time, co-occurrences of antibiotic resistance have been investigated for priority pathogens as defined by the WHO. For critically important pathogens, co-occurrences appear in plasmids, not in chromosomes, suggesting that the resistances may be epidemic and probably recent. These results hint at the need for new approaches to treating infections caused by critically important bacteria.202337511196