Colistin Resistance Mechanisms in Human and Veterinary Klebsiella pneumoniae Isolates. - Related Documents




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504901.0000Colistin Resistance Mechanisms in Human and Veterinary Klebsiella pneumoniae Isolates. Colistin (polymyxin E) is increasingly used as a last-resort antibiotic for the treatment of severe infections with multidrug-resistant Gram-negative bacteria. In contrast to human medicine, colistin is also used in veterinary medicine for metaphylaxis. Our objective was to decipher common colistin resistance mechanisms in Klebsiella pneumoniae isolates from animals. In total, 276 veterinary K. pneumoniae isolates, derived from companion animals or livestock, and 12 isolates from human patients were included for comparison. Six out of 276 veterinary isolates were colistin resistant (2.2%). Human isolates belonging to high-risk clonal lineages (e.g., ST15, ST101, ST258), displayed multidrug-resistant phenotypes and harboured many resistance genes compared to the veterinary isolates. However, the common colistin resistance mechanism in both human and animal K. pneumoniae isolates were diverse alterations of MgrB, a critical regulator of lipid A modification. Additionally, deleterious variations of lipopolysaccharide (LPS)-associated proteins (e.g., PmrB P95L, PmrE P89L, LpxB A152T) were identified. Phylogenetic analysis and mutation patterns in genes encoding LPS-associated proteins indicated that colistin resistance mechanisms developed independently in human and animal isolates. Since only very few antibiotics remain to treat infections with MDR bacteria, it is important to further analyse resistance mechanisms and the dissemination within different isolates and sources.202236421315
157210.9997Phenotypic and Genomic Characterization of AmpC-Producing Klebsiella pneumoniae From Korea. The prevalence of multidrug-resistant gram-negative bacteria has continuously increased over the past few years; bacterial strains producing AmpC β-lactamases and/or extended-spectrum β-lactamases (ESBLs) are of particular concern. We combined high-resolution whole genome sequencing and phenotypic data to elucidate the mechanisms of resistance to cephamycin and β-lactamase in Korean Klebsiella pneumoniae strains, in which no AmpC-encoding genes were detected by PCR. We identified several genes that alone or in combination can potentially explain the resistance phenotype. We showed that different mechanisms could explain the resistance phenotype, emphasizing the limitations of the PCR and the importance of distinguishing closely-related gene variants.201829611388
157320.9997Genomic Analysis of a Pan-Resistant Isolate of Klebsiella pneumoniae, United States 2016. Antimicrobial resistance is a threat to public health globally and leads to an estimated 23,000 deaths annually in the United States alone. Here, we report the genomic characterization of an unusual Klebsiella pneumoniae, nonsusceptible to all 26 antibiotics tested, that was isolated from a U.S. PATIENT: The isolate harbored four known beta-lactamase genes, including plasmid-mediated bla(NDM-1) and bla(CMY-6), as well as chromosomal bla(CTX-M-15) and bla(SHV-28), which accounted for resistance to all beta-lactams tested. In addition, sequence analysis identified mechanisms that could explain all other reported nonsusceptibility results, including nonsusceptibility to colistin, tigecycline, and chloramphenicol. Two plasmids, IncA/C2 and IncFIB, were closely related to mobile elements described previously and isolated from Gram-negative bacteria from China, Nepal, India, the United States, and Kenya, suggesting possible origins of the isolate and plasmids. This is one of the first K. pneumoniae isolates in the United States to have been reported to the Centers for Disease Control and Prevention (CDC) as nonsusceptible to all drugs tested, including all beta-lactams, colistin, and tigecycline.IMPORTANCE Antimicrobial resistance is a major public health threat worldwide. Bacteria that are nonsusceptible or resistant to all antimicrobials available are of major concern to patients and the public because of lack of treatment options and potential for spread. A Klebsiella pneumoniae strain that was nonsusceptible to all tested antibiotics was isolated from a U.S. PATIENT: Mechanisms that could explain all observed phenotypic antimicrobial resistance phenotypes, including resistance to colistin and beta-lactams, were identified through whole-genome sequencing. The large variety of resistance determinants identified demonstrates the usefulness of whole-genome sequencing for detecting these genes in an outbreak response. Sequencing of isolates with rare and unusual phenotypes can provide information on how these extremely resistant isolates develop, including whether resistance is acquired on mobile elements or accumulated through chromosomal mutations. Moreover, this provides further insight into not only detecting these highly resistant organisms but also preventing their spread.201829615503
158430.9997Molecular mechanisms and genomic basis of tigecycline-resistant Enterobacterales from swine slaughterhouses. The continuous emergence of tigecycline-resistant bacteria is undermining the effectiveness of clinical tigecycline. Environmental tigecycline-resistant bacteria have the potential to infect humans through human-environment interactions. Furthermore, the mechanisms of tigecycline resistance in Enterobacterales are complicated. In this study, we aimed to investigate the additional pathways of tigecycline resistance in environmental Enterobacterales besides tet(X) and tmexCD-toprJ. During the years 2019-2020, tigecycline-resistant Enterobacterales (n = 45) negative for tet(X) and tmexCD-toprJ were recovered from 328 different samples from two slaughterhouses. Five distinct bacteria species were identified, of which Klebsiella pneumoniae (n = 37) was the most common, with K. pneumoniae ST45 and ST35 being the predominant clones. Tigecycline resistance determinants analysis showed that tet(A) mutations and ramR inactivation were the most prevalent mechanisms for tigecycline resistance in the 45 strains. Two known tet(A) variants (type 1 and tet(A)-v) and one novel tet(A) variant (type 3) were identified. Cloning experiments confirmed that the novel type 3 tet(A) could enhance the 4-fold MIC for tigecycline. Inactivation of ramR was induced by either point mutations or indels of sequences, which could result in the overexpression of AcrAB pump genes leading to tigecycline resistance. In addition, all isolates were resistant to a wide range of antimicrobials and carried various resistance genes. These findings enriched the epidemiological and genomic characterizations of tigecycline-resistant Enterobacterales from slaughterhouses and contributed to a better understanding of the complex mechanisms of tigecycline resistance in environmental bacteria.202235985220
157440.9997Plethora of Resistance Genes in Carbapenem-Resistant Gram-Negative Bacteria in Greece: No End to a Continuous Genetic Evolution. Carbapenem-resistant Gram-negative bacteria are a public health threat that requires urgent action. The fact that these pathogens commonly also harbor resistance mechanisms for several other antimicrobial classes further reduces patient treatment options. The present study aimed to provide information regarding the multidrug resistance genetic background of carbapenem-resistant Gram-negative bacteria in Central Greece. Strains from a tertiary care hospital, collected during routine practice, were characterized using a DNA microarray-based assay. Various different resistance determinants for carbapenems, other beta-lactams, aminoglycosides, quinolones, trimethoprim, sulfonamides and macrolides were detected among isolates of the same sequence type. Eighteen different multidrug resistance genomic profiles were identified among the twenty-four K. pneumoniae ST258, seven different profiles among the eight K. pneumoniae ST11, four profiles among the six A. baumannii ST409 and two among the three K. oxytoca. This report describes the multidrug resistance genomic background of carbapenem-resistant Gram-negative bacteria from a tertiary care hospital in Central Greece, providing evidence of their continuous genetic evolution.202235056608
570050.9997Gram-negative bacterial colonization in the gut: Isolation, characterization, and identification of resistance mechanisms. BACKGROUND: The gut microbiome is made up of a diverse range of bacteria, especially gram-negative bacteria, and is crucial for human health and illness. There is a great deal of interest in the dynamic interactions between gram-negative bacteria and their host environment, especially considering antibiotic resistance. This work aims to isolate gram-negative bacteria that exist in the gut, identify their species, and use resistance-associated gene analysis to define their resistance mechanisms. METHODS: Samples were collected from all patients who had a stool culture at a tertiary care center in Lebanon. Each type of bacteria that was identified from the stool samples was subjected to critical evaluations, and all discovered strains underwent antimicrobial susceptibility testing. Polymerase chain reaction was used to profile the genes for Carbapenem-resistant Enterobacteriaceae (CRE), Extended-spectrum beta-lactamase (ESBL), and that of Pseudomonas aeruginosa strains. RESULTS: Escherichia coli, Klebsiella species, and Pseudomonas aeruginosa turned out to be the predominant microbiota members. Escherichia coli strains had a high frequency of extended-spectrum beta-lactamase genes, with the most discovered gene being bla CTX-M. Additionally, a considerable percentage of isolates had carbapenemase-resistant Enterobacteriaceae genes, suggesting the rise of multidrug-resistant strains. Multidrug resistance genes, such as bla mexR, bla mexB, and bla mexA, were found in strains of Pseudomonas aeruginosa, highlighting the possible difficulties in treating infections brought on by these bacteria. CONCLUSION: The findings highlight the critical importance of effective surveillance and response measures to maintain the effectiveness of antibiotics considering the introduction of multidrug resistance genes in Pseudomonas aeruginosa and ESBL and CRE genes in Escherichia coli.202439216133
569960.9997Presence of β-Lactamase Encoding Genes in Burkholderia cepacia Complex Isolated from Soil. Burkholderia cepacia complex has emerged as an important opportunistic bacteria group for immunocompromised patients, and it has a high level of intrinsic resistance for different antibiotic classes. Hydrolysis of β-lactam antibiotics by β-lactamases is the most common resistance mechanism in Gram-negative bacteria, and the presence of such enzymes complicates the selection of appropriate therapy. This study aimed at investigating the antimicrobial resistance profile and the presence of β-lactamase encoding genes in B. cepacia complex isolated from Brazilian soils. High-level ceftazidime resistance and several β-lactamase encoding genes were found, including the first report of bla(KPC) genes in bacteria isolated from soil.201828915359
502470.9997Colistin Resistance in Enterobacterales Strains - A Current View. Colistin is a member of cationic polypeptide antibiotics known as polymyxins. It is widely used in animal husbandry, plant cultivation, animal and human medicine and is increasingly used as one of the last available treatment options for patients with severe infections with carbapenem-resistant Gram-negative bacilli. Due to the increased use of colistin in treating infections caused by multidrug-resistant (MDR) bacteria, the resistance to this antibiotic ought to be monitored. Bacterial resistance to colistin may be encoded on transposable genetic elements (e.g. plasmids with the mcr genes). Thus far, nine variants of the mcr gene, mcr-1 - mcr-9, have been identified. Chromosomal resistance to colistin is associated with the modification of lipopolysaccharide (LPS). Various methods, from classical microbiology to molecular biology methods, are used to detect the colistin-resistant bacterial strains and to identify resistance mechanisms. The broth dilution method is recommended for susceptibility testing of bacteria to colistin. Colistin is a member of cationic polypeptide antibiotics known as polymyxins. It is widely used in animal husbandry, plant cultivation, animal and human medicine and is increasingly used as one of the last available treatment options for patients with severe infections with carbapenem-resistant Gram-negative bacilli. Due to the increased use of colistin in treating infections caused by multidrug-resistant (MDR) bacteria, the resistance to this antibiotic ought to be monitored. Bacterial resistance to colistin may be encoded on transposable genetic elements (e.g. plasmids with the mcr genes). Thus far, nine variants of the mcr gene, mcr-1 – mcr-9, have been identified. Chromosomal resistance to colistin is associated with the modification of lipopolysaccharide (LPS). Various methods, from classical microbiology to molecular biology methods, are used to detect the colistin-resistant bacterial strains and to identify resistance mechanisms. The broth dilution method is recommended for susceptibility testing of bacteria to colistin.201931880886
192080.9997Exploring the resistome, virulome, and mobilome of multidrug-resistant Klebsiella pneumoniae isolates: deciphering the molecular basis of carbapenem resistance. BACKGROUND: Klebsiella pneumoniae, a notorious pathogen for causing nosocomial infections has become a major cause of neonatal septicemia, leading to high morbidity and mortality worldwide. This opportunistic bacterium has become highly resistant to antibiotics due to the widespread acquisition of genes encoding a variety of enzymes such as extended-spectrum beta-lactamases (ESBLs) and carbapenemases. We collected Klebsiella pneumoniae isolates from a local tertiary care hospital from February 2019-February 2021. To gain molecular insight into the resistome, virulome, and genetic environment of significant genes of multidrug-resistant K. pneumoniae isolates, we performed the short-read whole-genome sequencing of 10 K. pneumoniae isolates recovered from adult patients, neonates, and hospital tap water samples. RESULTS: The draft genomes of the isolates varied in size, ranging from 5.48 to 5.96 Mbp suggesting the genome plasticity of this pathogen. Various genes conferring resistance to different classes of antibiotics e.g., aminoglycosides, quinolones, sulfonamides, tetracycline, and trimethoprim were identified in all sequenced isolates. The highest resistance was observed towards carbapenems, which has been putatively linked to the presence of both class B and class D carbapenemases, bla(NDM,) and bla(OXA), respectively. Moreover, the biocide resistance gene qacEdelta1 was found in 6/10 of the sequenced strains. The sequenced isolates exhibited a broad range of sequence types and capsular types. The significant antibiotic resistance genes (ARGs) were bracketed by a variety of mobile genetic elements (MGEs). Various spontaneous mutations in genes other than the acquired antibiotic-resistance genes were observed, which play an indirect role in making these bugs resistant to antibiotics. Loss or deficiency of outer membrane porins, combined with ESBL production, played a significant role in carbapenem resistance in our sequenced isolates. Phylogenetic analysis revealed that the study isolates exhibited evolutionary relationships with strains from China, India, and the USA suggesting a shared evolutionary history and potential dissemination of similar genes amongst the isolates of different origins. CONCLUSIONS: This study provides valuable insight into the presence of multiple mechanisms of carbapenem resistance in K. pneumoniae strains including the acquisition of multiple antibiotic-resistance genes through mobile genetic elements. Identification of rich mobilome yielded insightful information regarding the crucial role of insertion sequences, transposons, and integrons in shaping the genome of bacteria for the transmission of various resistance-associated genes. Multi-drug resistant isolates that had the fewest resistance genes exhibited a significant number of mutations. K. pneumoniae isolate from water source displayed comparable antibiotic resistance determinants to clinical isolates and the highest number of virulence-associated genes suggesting the possible interplay of ARGs amongst bacteria from different sources.202438664636
184890.9997Highly Colistin-resistant Aeromonas jandaei from a Human Blood Sample. Aeromonas species are Gram-negative rods known to cause infections such as gastroenteritis, bacteremia and wound infections. Colistin is one of few treatments for multidrug-resistant Gram-negative bacteria. However, colistin-resistant bacteria carrying the mobilized colistin resistance (mcr) gene are a threat in healthcare settings worldwide. In recent years, colistin-resistant Aeromonas species have been detected in environmental and clinical samples. We analyzed the genomic characteristics of one highly colistin-resistant A. jandaei isolated from a blood sample in Nepal, which harbored four novel mcr-like genes on its chromosome. Our study strongly suggests that A. jandaei is a reservoir of colistin-resistant genes. Inappropriate use of drugs in medicine and food production should be reduced and continued global surveillance for colistin-resistant bacteria is necessary.202338855938
2508100.9997Genetics of Acquired Antibiotic Resistance Genes in Proteus spp. Proteus spp. are commensal Enterobacterales of the human digestive tract. At the same time, P. mirabilis is commonly involved in urinary tract infections (UTI). P. mirabilis is naturally resistant to several antibiotics including colistin and shows reduced susceptibility to imipenem. However higher levels of resistance to imipenem commonly occur in P. mirabilis isolates consecutively to the loss of porins, reduced expression of penicillin binding proteins (PBPs) PBP1a, PBP2, or acquisition of several antibiotic resistance genes, including carbapenemase genes. In addition, resistance to non-β-lactams is also frequently reported including molecules used for treating UTI infections (e.g., fluoroquinolones, nitrofurans). Emergence and spread of multidrug resistant P. mirabilis isolates, including those producing ESBLs, AmpC cephalosporinases and carbapenemases, are being more and more frequently reported. This review covers Proteus spp. with a focus on the different genetic mechanisms involved in the acquisition of resistance genes to multiple antibiotic classes turning P. mirabilis into a dreadful pandrug resistant bacteria and resulting in difficult to treat infections.202032153540
1577110.9997Clonal Clusters, Molecular Resistance Mechanisms and Virulence Factors of Gram-Negative Bacteria Isolated from Chronic Wounds in Ghana. Wound infections are common medical problems in sub-Saharan Africa but data on the molecular epidemiology are rare. Within this study we assessed the clonal lineages, resistance genes and virulence factors of Gram-negative bacteria isolated from Ghanaian patients with chronic wounds. From a previous study, 49 Pseudomonas aeruginosa, 21 Klebsiellapneumoniae complex members and 12 Escherichia coli were subjected to whole genome sequencing. Sequence analysis indicated high clonal diversity with only nine P. aeruginosa clusters comprising two strains each and one E. coli cluster comprising three strains with high phylogenetic relationship suggesting nosocomial transmission. Acquired beta-lactamase genes were observed in some isolates next to a broad spectrum of additional genetic resistance determinants. Phenotypical expression of extended-spectrum beta-lactamase activity in the Enterobacterales was associated with bla(CTX-M-15) genes, which are frequent in Ghana. Frequently recorded virulence genes comprised genes related to invasion and iron-uptake in E. coli, genes related to adherence, iron-uptake, secretion systems and antiphagocytosis in P. aeruginosa and genes related to adherence, biofilm formation, immune evasion, iron-uptake and secretion systems in K. pneumonia complex. In summary, the study provides a piece in the puzzle of the molecular epidemiology of Gram-negative bacteria in chronic wounds in rural Ghana.202133810142
1919120.9997Combining Functional Genomics and Whole-Genome Sequencing to Detect Antibiotic Resistance Genes in Bacterial Strains Co-Occurring Simultaneously in a Brazilian Hospital. (1) Background: The rise of multi-antibiotic resistant bacteria represents an emergent threat to human health. Here, we investigate antibiotic resistance mechanisms in bacteria of several species isolated from an intensive care unit in Brazil. (2) Methods: We used whole-genome analysis to identify antibiotic resistance genes (ARGs) and plasmids in 34 strains of Gram-negative and Gram-positive bacteria, providing the first genomic description of Morganella morganii and Ralstonia mannitolilytica clinical isolates from South America. (3) Results: We identified a high abundance of beta-lactamase genes in resistant organisms, including seven extended-spectrum beta-lactamases (OXA-1, OXA-10, CTX-M-1, KPC, TEM, HYDRO, BLP) shared between organisms from different species. Additionally, we identified several ARG-carrying plasmids indicating the potential for a fast transmission of resistance mechanism between bacterial strains. Furthermore, we uncovered two pairs of (near) identical plasmids exhibiting multi-drug resistance. Finally, since many highly resistant strains carry several different ARGs, we used functional genomics to investigate which of them were indeed functional. In this sense, for three bacterial strains (Escherichia coli, Klebsiella pneumoniae, and M. morganii), we identified six beta-lactamase genes out of 15 predicted in silico as those mainly responsible for the resistance mechanisms observed, corroborating the existence of redundant resistance mechanisms in these organisms. (4) Conclusions: Systematic studies similar to the one presented here should help to prevent outbreaks of novel multidrug-resistant bacteria in healthcare facilities.202133920372
1579130.9997Inverse Association between the Existence of CRISPR/Cas Systems with Antibiotic Resistance, Extended Spectrum β-Lactamase and Carbapenemase Production in Multidrug, Extensive Drug and Pandrug-Resistant Klebsiella pneumoniae. Antimicrobial resistance, with the production of extended-spectrum β-lactamases (ESBL) and carbapenemases, is common in the opportunistic pathogen, Klebsiella pneumoniae. This organism has a genome that can contain clustered regularly interspaced short palindromic repeats (CRISPRs), which operate as a defense mechanism against external invaders such as plasmids and viruses. This study aims to determine the association of the CRISPR/Cas systems with antibiotic resistance in K. pneumoniae isolates from Iraqi patients. A total of 100 K. pneumoniae isolates were collected and characterized according to their susceptibility to different antimicrobial agents. The CRISPR/Cas systems were detected via PCR. The phenotypic detection of ESBLs and carbapenemases was performed. The production of ESBL was detected in 71% of the isolates. Carbapenem-resistance was detected in 15% of the isolates, while only 14% were susceptible to all antimicrobial agents. Furthermore, the bacteria were classified into multidrug (77%), extensively drug-resistant (11.0%) and pandrug-resistant (4.0%). There was an inverse association between the presence of the CRISPR/Cas systems and antibiotic resistance, as resistance was higher in the absence of the CRISPR/Cas system. Multidrug resistance in ESBL-producing and carbapenem-resistant K. pneumoniae occurred more frequently in strains negative for the CRISPR/Cas system. Thus, we conclude that genes for exogenous antibiotic resistance can be acquired in the absence of the CRISPR/Cas modules that can protect the bacteria against acquiring foreign DNA.202337370299
1570140.9997Genomic Insights into Two Colistin-Resistant Klebsiella pneumoniae Strains Isolated from the Stool of Preterm Neonate During the First Week of Life. Background: Klebsiella pneumoniae is a major opportunistic pathogen frequently associated with nosocomial infections, and often poses a major threat to immunocompromised patients. In our previous study, two K. pneumoniae (K36 and B13), which displayed resistance to almost all major antibiotics, including colistin, were isolated. Both isolates were not associated with infection and isolated from the stools of two preterm neonates admitted to the neonatal intensive care unit (NICU) during their first week of life. Materials and Methods: In this study, whole genome sequencing was performed on these two clinical multidrug resistant K. pneumoniae. We aimed to determine the genetic factors that underline the antibiotic-resistance phenotypes of these isolates. Results: The strains harbored bla(SHV-27), bla(SHV-71), and oqxAB genes conferring resistance to cephalosporins, carbapenems, and fluoroquinolones, respectively, but not harboring any known plasmid-borne colistin resistance determinants such as mcr-1. However, genome analysis discovered interruption of mgrB gene by insertion sequences gaining insight into the development of colistin resistance. Conclusion: The observed finding that points to a scenario of potential gut-associated resistance genes to Gram negative (K. pneumoniae) host in the NICU environment warrants attention and further investigation.202031545116
1689150.9997Occurrence and Characteristics of Mcrs among Gram-Negative Bacteria Causing Bloodstream Infections of Infant Inpatients between 2006 and 2019 in China. The aim of this study was to determine the occurrence of mobilized colistin resistance (mcr) genes in Gram-negative bacteria causing bloodstream infections of child inpatients in China. Bacteria were collected between 2006 and 2019 in a maternal and child health hospital, and mcr genes were screened by PCR. Five of 252 isolates were mcr-positive, including one mcr-1-positive colistin-resistant Escherichia coli isolate, two mcr-9-positive colistin-susceptible Salmonella enterica isolates, and two mcr-9-positive colistin-susceptible Enterobacter hormaechei isolates. These were obtained from two neonate and three infant patients admitted between 2009 and 2018. The E. coli isolate was obtained from a neonate aged 20 min, suggestive of a possible mother-to-neonate transmission. The five mcr-positive isolates were multidrug resistant, and two S. enterica and one E. hormaechei isolate showed a hypervirulent phenotype compared to a hypervirulent Klebsiella pneumoniae type strain in a Galleria mellonella infection model. The mcr-1 gene was carried by an IncX4-type pA1-like epidemic plasmid, and the mcr-9 gene was detected on IncHI2/2A-type novel plasmids co-carrying multiple resistance genes. The four IncHI2/2A-type plasmids shared a backbone and a high similarity (≥77% coverage and ≥ 90% nucleotide identity), suggesting that they were derived from a common ancestor with cross-species transmission and have circulated locally over a long period. The conjugation assay showed that the mcr-1-encoding plasmid and one mcr-9-encoding plasmid were self-transmissible to E. coli with high conjugation frequencies. Our findings demonstrate that mcr genes have disseminated in the community and/or hospitals, mediated by epidemic/endemic plasmids over a long period. The study shows that continuous monitoring of mcr genes is imperative for understanding and tackling their dissemination. IMPORTANCE Antimicrobial resistance, especially the spread of carbapenemase-producing Enterobacteriaceae (CPE), represents one of the largest challenges to One Health coverage of environmental, animal, and human sectors. Colistin is one of the last-line antibiotics for clinical treatment of CPE. However, the emergence of the mobilized colistin resistance (mcr) gene largely threatens the usage of colistin in the clinical setting. In this study, we investigated the existence of mcr genes in 252 Gram-negative bacteria collected between 2006 and 2019 which caused bloodstream infections of child inpatients in China. We found a high prevalence of mcr carriage among children inpatients in the absence of professional exposure, and mcr might have widely disseminated in the community via different routes. This study emphasizes the importance of rational use of colistin in the One Health frame, and highlights both the urgent need for understanding the prevalence and dissemination of mcr genes in different populations and the importance of effective measures to control their spread.202235138190
1847160.9997Resistance to Carbapenems in Non-Typhoidal Salmonella enterica Serovars from Humans, Animals and Food. Non-typhoidal serovars of Salmonella enterica (NTS) are a leading cause of food-borne disease in animals and humans worldwide. Like other zoonotic bacteria, NTS have the potential to act as reservoirs and vehicles for the transmission of antimicrobial drug resistance in different settings. Of particular concern is the resistance to critical "last resort" antimicrobials, such as carbapenems. In contrast to other Enterobacteriaceae (e.g., Klebsiella pneumoniae, Escherichia coli, and Enterobacter, which are major nosocomial pathogens affecting debilitated and immunocompromised patients), carbapenem resistance is still very rare in NTS. Nevertheless, it has already been detected in isolates recovered from humans, companion animals, livestock, wild animals, and food. Five carbapenemases with major clinical importance-namely KPC (Klebsiella pneumoniae carbapenemase) (class A), IMP (imipenemase), NDM (New Delhi metallo-β-lactamase), VIM (Verona integron-encoded metallo-β-lactamase) (class B), and OXA-48 (oxacillinase, class D)-have been reported in NTS. Carbapenem resistance due to the production of extended spectrum- or AmpC β-lactamases combined with porin loss has also been detected in NTS. Horizontal gene transfer of carbapenemase-encoding genes (which are frequently located on self-transferable plasmids), together with co- and cross-selective adaptations, could have been involved in the development of carbapenem resistance by NTS. Once acquired by a zoonotic bacterium, resistance can be transmitted from humans to animals and from animals to humans through the food chain. Continuous surveillance of resistance to these "last resort" antibiotics is required to establish possible links between reservoirs and to limit the bidirectional transfer of the encoding genes between S. enterica and other commensal or pathogenic bacteria.201829642473
1702170.9997Molecular Epidemiology and Antimicrobial Resistance of Outbreaks of Klebsiella pneumoniae Clinical Mastitis in Chinese Dairy Farms. Klebsiella pneumoniae is an opportunistic pathogen that causes serious infections in humans and animals. However, the availability of epidemiological information on clinical mastitis due to K. pneumoniae is limited. To acquire new information regarding K. pneumoniae mastitis, data were mined about K. pneumoniae strains on dairy cattle farms (farms A to H) in 7 Chinese provinces in 2021. Hypermucoviscous strains of K. pneumoniae were obtained by the string test. MICs of antimicrobial agents were determined via the broth microdilution method. Ten antimicrobial resistance genes and virulence genes were identified by PCR. The prevalence of K. pneumoniae was 35.91% (65/181), and 100% of the bacteria were sensitive to enrofloxacin. Nine antimicrobial resistance genes and virulence genes were identified and compared among farms. The hypermucoviscous phenotype was present in 94.44% of isolates from farm B, which may be a function of the rmpA virulence gene. Based on these data, the multidrug-resistant strains SD-14 and HB-21 were chosen and sequenced. Genotypes were assayed for K. pneumoniae isolates from different countries and different hosts using multilocus sequence typing (MLST). Ninety-four sequence types (STs) were found, and 6 STs present a risk for spreading in specific regions. Interestingly, ST43 was observed in bovine isolates for the first time. Our study partially reveals the current distribution characteristics of bovine K. pneumoniae in China and may provide a theoretical basis for the prevention and treatment of bovine K. pneumoniae mastitis. IMPORTANCE K. pneumonia is ubiquitous in nature and infects a wide range of hosts, including animals, and humans. It is one of the leading inducements of clinical mastitis (CM) in dairy cows, a prevalent and costly disease that is predominantly associated with bacterial infection. In general, CM caused by Gram-negative bacteria is more difficult to cure than that associated with Gram-positive pathogens, with an average cost per case of 211.03 U.S. dollars (USD) for Gram-negative bacterial infections compared with 133.73 USD for Gram-positive bacterial CM cases. After Escherichia coli, K. pneumoniae is the second most common Gram-negative cause of bovine CM, but it is the most detrimental in terms of decreased milk yield, discarded milk, treatment costs, death, and culling. In view of the economic implications of K. pneumoniae infection in dairy farming, research into population structure and antibiotic resistance is particularly important.202236374018
4951180.9997Aeromonas and mcr-3: A Critical Juncture for Transferable Polymyxin Resistance in Gram-Negative Bacteria. Polymyxin antibiotics B and colistin are considered drugs of last resort for the treatment of multi-drug and carbapenem-resistant Gram-negative bacteria. With the emergence and dissemination of multi-drug resistance, monitoring the use and resistance to polymyxins imparted by mobilised colistin resistance genes (mcr) is becoming increasingly important. The Aeromonas genus is widely disseminated throughout the environment and serves as a reservoir of mcr-3, posing a significant risk for the spread of resistance to polymyxins. Recent phylogenetic studies and the identification of insertion elements associated with mcr-3 support the notion that Aeromonas spp. may be the evolutionary origin of the resistance gene. Furthermore, mcr-3-related genes have been shown to impart resistance in naïve E. coli and can increase the polymyxin MIC by up to 64-fold (with an MIC of 64 mg/L) in members of Aeromonas spp. This review will describe the genetic background of the mcr gene, the epidemiology of mcr-positive isolates, and the relationship between intrinsic and transferable mcr resistance genes, focusing on mcr-3 and mcr-3-related genes.202439599474
1917190.9997Prediction of major antibiotic resistance in Escherichia coli and Klebsiella pneumoniae in Singapore, USA and China using a limited set of gene targets. Antibiotic resistance in Gram-negative bacteria, especially Enterobacteriaceae, can be conferred by a large number of different acquired resistance genes, although it appears that relatively few dominate. A previous survey of Escherichia coli and Klebsiella pneumoniae isolates from Sydney, Australia, revealed that a limited set of genes could reliably predict resistance to third-generation cephalosporins (3GCs) and aminoglycosides. Here we tested E. coli and K. pneumoniae isolates with a cefotaxime, ceftriaxone and/or ceftazidime minimum inhibitory concentration of ≥ 2 μg/mL from China and Singapore, with significantly higher resistance rates than Australia, as well as the USA. Few targets were needed to predict non-susceptibility to 3GCs (95/95; 100%) and gentamicin (47/51; 92%). The gene types detected here are consistent with previous surveys in similar countries with similar resistance rates, where the majority of 3GC resistance can be explained by blaCTX-M genes. This study identified a limited set of genes capable of predicting resistance to 3GC and aminoglycoside antibiotics and implies a restriction in the global resistance gene pool that can be exploited for diagnostic purposes.201424721234