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PubMed2026

Genomic surveillance reveals escalating antimicrobial resistance and plasmid diversity in clinical Salmonella 1,4,[5],12:i:- ST34 isolates from Guizhou Province, China.

INTRODUCTION: Salmonella 1,4,[5],12:i:- ST34 has emerged as a significant public health issue due to its association with various antimicrobial resistance genes (ARGs) and transferable plasmids. However, its genomic characteristics and potential influence on public health in Guizhou have not been comprehensively assessed. METHODS: From 2019 to 2023, a 5-year surveillance was conducted in nine cities (prefectures) of Guizhou Province. We integrated phenotypic and genomic analyses of 281 clinical Salmonella 1,4,[5],12:i:- ST34 isolates to investigate the prevalence of ARGs and plasmids and to analyze the molecular epidemiology and evolution. RESULTS: The isolates exhibited resistance to first-line antibiotics, with 22.4% for ciprofloxacin, 11.4% for azithromycin, 18.5% for ceftazidime, and 39.1% for cefotaxime. ARGs showed substantial agreement with phenotypes for tetracycline, macrolides, third-generation cephalosporins (3GCs), carbapenems, and colistin (80.8-100.0% consistency; Kappa: 0.50-1.00). Plasmid analysis identified IncQ1 (84.3%) and IncHI2/IncHI2A (26.3%) as the main replicons, with the variety of plasmid replicons increasing from 7 to 21 over the 5 years. ARGs associated with resistance to critically important antibiotics (CIAs) were frequently predicted to be located on plasmid-associated contigs, with significant associations observed between IncHI2/IncHI2A plasmids and ARGs conferring resistance to fluoroquinolones, macrolides, and cephalosporins (P < 0.05). Molecular typing divided 281 isolates into 37 cgSTs, with cgST52428 being the most common. Molecular epidemiological analysis revealed that Guizhou isolates primarily clustered together, sharing close genetic ties with those from Sichuan and Guangdong, and exhibited the highest genetic similarity to pork-derived isolates. Phylogenetic analysis revealed clustering of CIA-resistant ARGs and plasmids in Clades 4 and 5, with a significant association between IncHI2/IncHI2A plasmids and CIA-resistant ARGs (χ2 = 112.12, P < 0.001). Additionally, class 1 integron was associated with higher ARG burdens, while virulence-associated genes were conserved and predominantly chromosome-associated. Gene-content analysis revealed that isolates in Clades 4 and 5 harbored the largest mean gene complements, and cgST52428 isolates also harbored the largest among dominant cgSTs. DISCUSSION: This study presents a comprehensive genomic profile of Salmonella 1,4,[5],12:i:- ST34 in Guizhou, providing essential data for exploring the resistance characteristics and investigating the molecular epidemiology of Salmonella 1,4,[5],12:i:-.

ST34↗

PubMed2026

Carbapenem-resistant Gram-negative pathogens: molecular epidemiology, diagnostic advances, and emerging therapeutic strategies.

Carbapenem-resistant Gram-negative pathogens (CR-GNPs) have become an important global health problem, contributing significantly to healthcare-associated infections, extended hospital stays, high mortality rates, and higher healthcare costs. The dissemination of carbapenem resistance is mainly attributed to the spread of carbapenemase-encoding genes, such as the Klebsiella pneumoniae carbapenemase (KPC), the New Delhi metallo-β-lactamase (NDM), the Verona integron-encoded metallo-β-lactamase (VIM), the imipenemase (IMP), and the oxacillinase-48 (OXA-48)-like enzymes associated with clinically important Gram-negative pathogens, including Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa. As well as carbapenemase production, resistance can also develop via alteration of porins, upregulation of efflux pumps, and the buildup of several resistance factors, generating highly adaptable and hard-to-treat microbes. Phenotypic resistance patterns may not predict the underlying mechanism and accurate laboratory detection remains challenging. The identification and monitoring of carbapenem-resistant organisms have undergone improvement in recent years thanks to molecular diagnostics, rapid phenotypic tests, whole-genome sequencing and metagenomics. At the same time, new drugs have been developed, such as ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, cefiderocol and combinations of aztreonam, offering increased treatment options, but with emerging resistance an issue. This mini review covers the molecular epidemiology of CR-GNPs, the latest developments and challenges in diagnosing these infections, new therapeutic options, and future perspectives on genomic surveillance, antimicrobial stewardship, and precision medicine strategies to address the increasing threat of carbapenem resistance.

Gram-negative pathogens↗

PubMed2025

Reduction in ARGs and Mobile Genetic Elements Using 2-Bromoethane Sulfonate in an MFC-Powered Fenton System.

The integration of an MFC-powered Fenton (MFC-Fenton) system into the traditional anaerobic composting process can promote excess dewatered sludge (ES) decomposition. However, the antibiotic resistance gene (ARG) profiles in ES treated by MFC-Fenton systems remain poorly understood; in addition, the effect of adding 2-bromoethane sulfonate (BES, a methane inhibitor) during ES treatment using an MFC-Fenton system on ARG levels is largely unexplored. The present work focused on investigating the effects of BES and bioelectrochemical processes on ARG and MGE abundances and unraveling the ARG attenuation mechanism. According to our findings, adding BES promoted ARG reduction in ES in an MFC-Fenton system. The average ARG levels in the MFC-Fenton samples containing high BES contents (0.4 or 0.5 g BES/g VSS) markedly declined relative to those in samples containing lower BES levels. Moreover, macrolide transporter ATP-binding protein, macrolide-efflux protein, and macB levels markedly decreased as BES levels increased. BES supplementation and bioelectrochemical assistance were crucial for altering the ARG composition in the MFC-Fenton system. Changes in the microbial community composition had the greatest effect on the variation in ARG composition. Furthermore, the Actinobacteria and Firmicutes levels accounted for 52.8% of the overall ARG variation. Among MGEs, plasmids, insertion sequences, and integrons showed lower levels within the sludge metagenomes. Typically, sulI, sulII, tetG, and bla TEM levels were positively correlated with metal resistance genes (MRGs), and their levels markedly declined following the MFC-Fenton process. Thus, the collective evidence indicates that BES synergizes with bioelectrogenesis to reduce ARG abundance.

Sewage↗

PubMed2004

Characterization of antimicrobial-resistant phenotypes and genotypes among Salmonella enterica recovered from pigs on farms, from transport trucks, and from pigs after slaughter.

The main objectives of this study were to determine antimicrobial resistance patterns among Salmonella serotypes and to evaluate the role of transport trucks in dissemination of antimicrobial-resistant strains of Salmonella. Salmonella from groups of nursery and finishing pigs on farms, from trucks, and from pigs after slaughter were compared using serotyping, patterns of antimicrobial resistance, and pulsed-field gel electrophoresis patterns. The five farms included in the study yielded 858 isolates representing 27 Salmonella serovars. The most common resistance observed (80% of all isolates) was to tetracycline; resistance to ampicillin (42%), chloramphenicol (31%), amoxicillin/clavulanic acid (30%), and piperacillin (31%) also were common. We found a correlation between serovar and antimicrobial resistance. High correlation was found between Salmonella Typhimurium var. Copenhagen and chloramphenicol resistance (Spearman rank correlation, rho = 0.7). Multidrug resistance was observed primarily in Salmonella Typhimurium var. Copenhagen (94%) and Salmonella Typhimurium (93%) and was much less common in the other common serovars, including Salmonella Derby (7%) and Salmonella Heidelberg (8%). Of the 225 isolates exhibiting the most common pentaresistance pattern in this study, amoxicillin/clavulanic acid-ampicillin-chloramphenicol-piperacillin-tetracycline, 220 (98%) were Salmonella Typhimurium var. Copenhagen, and 86% of the isolates of this serovar had this pattern. Isolates from the trucks were similar, based on pulsed-field gel electrophoresis patterns, to those from the cecum and mesenteric lymph nodes of pigs on two of the farms, suggesting the probable infection of pigs during transport. Class I integrons were also common among various serovars.

Animals↗

PubMed2005

Multidrug-resistant Klebsiella pneumoniae isolated from farm environments and retail products in Oklahoma.

Multidrug-resistant enteric bacteria were isolated from turkey, cattle, and chicken farms and retail meat products in Oklahoma. Among the isolated species, multidrug-resistant Klebsiella pneumoniae was prevalently isolated from most of the collected samples. Therefore, a total of 132 isolates of K. pneumoniae were characterized to understand their potential roles in the dissemination of antibiotic-resistance genes in the food chains. Multidrug-resistant K. pneumoniae was most frequently recovered from a turkey farm and ground turkey products among the tested samples. All isolates were resistant to ampicillin, tetracycline, streptomycin, gentamycin, and kanamycin. Class 1 integrons located in plasmids were identified as a common carrier of the aadA1 gene, encoding resistance to streptomycin and spectinomycin. Production of beta-lactamase in the K. pneumoniae isolates played a major role in the resistance to beta-lactam agents. Most isolates (96%) possessed bla(SHV1). Five strains were able to express both SHV-11 (pI 6.2) and TEM-1 (pI 5.2) beta-lactamase. Transfer of these antibiotic-resistance genes to Escherichia coli was demonstrated by transconjugation. The bacterial genomic DNA restriction patterns by pulsed-field gel electrophoresis showed that the same clones of multidrug-resistant K. pneumoniae remained in feathers, feed, feces, and drinking water in turkey environments, indicating the possible dissemination of antibiotic-resistance genes in the ecosystem and cross-contamination of antibiotic-resistant bacteria during processing and distribution of products.

Animal Husbandry↗

PubMed2006

Antimicrobial resistance types and genes in Salmonella enterica infantis isolates from retail raw chicken meat and broiler chickens on farms.

Salmonella enterica subsp. enterica serotype Infantis isolates from retail raw chicken meat (n = 98) and broiler chickens on farms (n = 70) were examined for antimicrobial susceptibility and antimicrobial resistance genes. A total of 15 antimicrobial resistance types, 14 in meat and 10 in broiler isolates, were identified, and 9 of the 15 types were indistinguishable between meat and broiler isolates. Resistance to both oxytetracycline and dihydrostreptomycin accounted for 94.0% of the resistance types in meat and broiler isolates, and each type harbored aadA1 within 1.0 kb of class 1 integron and tetA. Of nalidixic acid resistance types, point mutations at 87Asp (GAC) to Tyr (TAC) in the quinolone resistance-determining region of gyrA was detected in 10 of 13 meat isolates and at 87Asp to Asn (AAC) in four of seven broiler isolates. These findings suggest that the antimicrobial resistance of Salmonella Infantis in retail chicken meat predominantly originates from broiler chickens.

Animals↗

PubMed1999

OXA-type beta-lactamases.

The OXA-type (oxacillin-hydrolysing) enzymes are widespread and have been mostly described in Enterobacteriaceae and in P. aeruginosa. They usually confer resistance to amino- and ureidopenicillin and possess high-level hydrolytic activity against cloxacillin, oxacillin, and methicillin. Their activities are weakly inhibited by clavulanic acid but sodium chloride (NaCl) possesses a strong inhibition activity. Oxacillin-hydrolysing b-lactamases belong to Ambler class D and thus possess an active serine site as classes A and C b-lactamases. Overall amino-acid identities between class D and class A or class C b-lactamases is about 16%. Until now, 24 Ambler class D enzymes, named OXA-1 to OXA-22, AmpS and LCR-1, have been characterised, either by sequence and/or by biochemical analyses, but for none of them a three dimensional structure is yet available. While some oxacillinases present a significant degree of amino-acid identity (for example, OXA-1 and OXA-4; OXA-10 (PSE-2) derivatives; OXA-2 and OXA-3), most of them are only weakly related (20% to 30% amino-acid identity). Oxacillinases usually display a restricted-spectrum phenotype. However extension of their spectrum towards oxyimino cephalosporins and/or imipenem has recently been observed mostly as a consequence of point mutations in OXA-2 or OXA-10 derivatives. Their frequent plasmid- and/or integron-location provide them a mean for a wide diffusion.

Amino Acid Sequence↗

PubMed1998

Evolution of bacterial resistance to antibiotics during the last three decades.

Bacterial resistance to antibiotics is often plasmid-mediated and the associated genes encoded by transposable elements. These elements play a central role in evolution by providing mechanisms for the generation of diversity and, in conjunction with DNA transfer systems, for the dissemination of resistances to other bacteria. At the University Hospital of Zaragoza, extensive efforts have been made to define both the dissemination and evolution of antibiotic resistance by studying the transferable R plasmids and transposable elements. Here we describe the research on bacterial resistance to antibiotics in which many authors listed in the references have participated. The aspects of bacterial resistance dealt with are: (i) transferable resistance mediated by R plasmids in Gram-negative bacteria, (ii) R plasmid-mediated resistance to apramycin and hygromycin in clinical strains, (iii) the transposon Tn1696 and the integron In4, (iv) expression of Escherichia coli resistance genes in Haemophilus influenzae, (v) aminoglycoside-modifying-enzymes in the genus Mycobacterium with no relation to resistance, and (vi) macrolide-resistance and new mechanisms developed by Gram-positive bacteria.

Anti-Bacterial Agents↗

PubMed2001

[Molecular biology of the mechanism of acquisition of antimicrobial-resistance].

There are two ways for a bacterium to acquire antimicrobial-resistance: 1) Horizontal transfer of resistance gene(s) from outside, 2) Mutation of its own chromosome. The former case includes conjugation, transduction and transformation. Resistance genes usually locate on transposon or integron and have inverted or direct repeats on both sides, or link to a special sequence at one side. A target of an antibiotic is an essential enzyme for the bacterium to survive, and the corresponding gene is located on the chromosome. The mutation of the essential gene may cause resistance to antimicrobials by decreasing the affinity of enzyme to the drug. The mutation of genes for drug influx or efflux also causes antimicrobial resistance.

Bacteria↗

PubMed2001

[Metallo-beta-lactamase producing bacteria].

Metallo-beta-lactamases are the carbapenemases belonging to the class B beta-lactamases on a molecular level. Two types of the metallo-beta-lactamase, IMP-1 and VIM-1, which have been detected mainly from Pseudomonas aeruginosa, respectively, in Japan and in Europe are especially important, because of the broad substrate specificity. These enzymes confer resistance to not only the carbapenems but also almost all beta-lactam antibiotics expect for monobactams. Clinical strains producing IMP-1 type enzymes are easily detectable by the PCR method or by the double-disk method using the enzyme inhibitor of mercapto-compound and the substrate antibiotic such as imipenem or ceftazidime. The gene blaIMP is frequently identified as a cassette inserted in the integron structure on the transmissible plasmids, disseminating among various gram-negative bacteria.

Bacteria↗

PubMedDate not supplied

Characterization of antibiotic-resistant bacteria in rendered animal products.

Antibiotics are used in food animal production to treat diseases and also to improve performance. Antibiotics are not used on all farms, and antibiotic resistance is occasionally found on farms that do not use antibiotics. Rendered animal protein products are often included in poultry feeds and could potentially serve as a source of antibiotic-resistant bacteria. One hundred sixty-five rendered animal protein products from cattle, poultry, and fish were aseptically collected from poultry feed mills. Fifty-five percent of the poultry meal samples had detectable levels of gram-negative bacteria ranging from 40 to 10,440 colony-forming units/g of sample. Poultry meal and meat and bone meal had the greatest number of samples with bacteria resistant to five or more antibiotics. A high percentage of feed samples (85%) contained bacteria resistant to amoxicillin, ampicillin, clavulanic acid, or cephalothin, whereas few samples contained bacteria resistant to ciprofloxacin, kanamycin, or trimethoprim/sulfamethoxazole. Acinetobacter calcoaceticus, Citrobacter freundii, and Enterobacter cloacae were the most commonly isolated antibiotic-resistant bacteria. Isolation for Salmonella was also performed, with 14% of the meat and bone meal samples containing Salmonella sp. Only one of the meat and bone meal isolates, Salmonella livingstone, was resistant to five or more antibiotics. Many of the antibiotic-resistant bacteria contained integrons, genetic elements that mediate multiple drug resistance.

Animal Feed↗

PubMed2002

Occurrence and characterization of resistance to extended-spectrum cephalosporins mediated by beta-lactamase CMY-2 in Salmonella isolated from food-producing animals in Canada.

Resistance of Salmonella to extended-spectrum cephalosporins (ESCs) is being reported with increasing frequency. In humans, infections with Salmonella resistant to ESCs threaten the efficacy of ceftriaxone, the drug of choice for treating salmonellosis in children. To determine the occurrence of resistance to ESCs, we examined 8426 strains isolated from food-producing animals in Canada in 1994-99 for reduced susceptibility or resistance to ceftriaxone. Of the 8 such strains identified (7 from turkeys and 1 from cattle), 5 had reduced susceptibility, and 3 were resistant; 2 were isolated in 1995, 1 was isolated in each of 1996 and 1997, and 4 were isolated in 1999. Isoelectric focusing showed that all 8 isolates produced a beta-lactamase with a pI > or = 9. The strains were resistant to cefoxitin and not inhibited by clavulanic acid. Primers specific for the Citrobacter freundii blaAmpC gene produced the expected product in the polymerase chain reaction. DNA sequencing showed that all isolates possessed the blaCMY-2 gene. Plasmid DNA from all 8 isolates transformed Escherichia coli DH10B, whereas only 1 isolate transferred blaCMY-2 conjugally. All transformants and the transconjugant were resistant to ampicillin, cefoxitin, ceftiofur, cephalothin, streptomycin, sulfisoxazole, and tetracycline. Southern blots of plasmids from the isolates, the transformants, and the transconjugant showed that blaCMY-2 was located on similar-sized plasmids (60 or 90 MDa) in the transformants and the transconjugant. In the S. Typhimurium DT104 and S. Ohio isolates, the floSt gene was found on the same plasmid. Class 1 integrons with the aadB gene cassette were detected in the S. Bredeney isolates but not in their transformants or the transconjugant. Pulsed-field gel electrophoresis and plasmid profiles indicated that both clonal dispersion and horizontal transfer of blaCMY-2 may have caused dissemination of the resistance determinant.

Alberta↗

PubMed2003

The molecular characterisation of the extended spectrum beta-lactamase (ESBL) producing strain of Salmonella enterica serovar Mbandaka isolated in Poland.

The molecular attributes of the first ESBL producing isolate 267/99 of Salmonella enterica serovar Mbandaka isolated in 1999 in Poland were characterised. Tested strain produced CTX-M-3 and TEM-1 beta-lactamases, encoded by genes localised on the about 80 kb self-transferable plasmid, harbouring the 2 kb class 1 integron carrying aadA2 gene.

Anti-Bacterial Agents↗

PubMed2003

[Evolution of bacterial resistance to antibiotics].

Drug Resistance, Bacterial↗

PubMed2005

[Integration and expression of sdh gene in Escherichia coli].

The chloramphenicol-resistant cassette with short shared sequences of ptsG gene on both ends was PCR-generated from plasmid pKF3 and ligated to pMD18-T to construct pMD18-PC. The sdh gene for sorbose dehydrogenase was generated from plasmid pQE60-SDH and inserted into pMD18-PC, then pMD18-PC-SDH was constructed. It was digested with Pvu II and the target fragment ptsG1-cat-sdh-ptsG2 was recovered and electroporated into Escherichia coli JM109/pKD46. Homologous-recombination between linear DNA cassettes and Escherichia coli chromosomes took place by Red recombination. The detection result showed that the integron JM109s was of sorbose dehydrogenase activity. The PCR products assay using the upstream and downstream sequences of ptsG gene as primers and JM109s genomic DNA as template, indicated that sdh gene had been integrated at the ptsG gene site in Escherichia coli.

Anti-Bacterial Agents↗

PubMed2004

[How bacteria resist antibiotics: a primary form of collective intelligence?].

Bacteria produce inhibitory enzymes (beta-lactamases, etc), block antibiotic attachment to target molecules (MRSA, etc.), extrude antibiotics from the cell by active efflux systems (multidrug resistant pseudomonas, etc) or limit antibiotic penetration through the outer membrane in Gram negatives. Genetically, resistance occurs after mutation or horizontal transfers (transformation, transduction, conjugation) of mobile genetic elements (integrons, transposons, phages, plasmids), associated with a risk of epidemic spread. Recent data stress the importance pheromones for facilitating inter-bacterial genetic exchanges. Activated by quinolones and penicillins the SOS response augments the mutation rate (by about 10,000 fold) and liberates mobile genetic elements offering more opportunities to select resistance. These highly pertinent non-darwinian systems raise the hypothesis of a primary form of intelligence developed already 3.8 billions years ago.

Anti-Bacterial Agents↗

PubMed2005

[Study on the genetic structure and transmission mechanism of a plasmid-mediated AmpC beta-lactamase].

OBJECTIVE: To clone the gene of plasmid-mediated AmpC beta-lactamase from the plasmid of multiple-drug resistance Klebsiella pneumoniae producing plasmid-mediated AmpC beta-lactamase and demonstrate its mechanism of transmission. METHODS: Plasmids of the transconjugant were extracted and digested with restriction endonuclease HindIII. Taq DNA polymerase was applied to fill the recessed 3' termini, and a single deoxyadenosine was added to the 3' termimi of fragments. Then these fragments were ligated with pGEM-T Easy vector. E. coli DH5alpha containing recombinant plasmid was selected on MacConkey agar plates containing ampicillin and cefoxitin. Insert fragments were sequenced by primer walking. MIC determinations and isoelectric focusing electrophoresis (IFE) were utilized to analyze recombinant. RESULTS: The recombinant plasmid pT948 containing a 5.2-kb insert was obtained. The inserted fragment contained a bla(DHA-1) and a regulatory gene ampR. The insertion sequence (IS26), qacEDelta1 and sulI genes of the I type integron were obtained near the bla(DHA-1) gene. Recombinant expressed a beta-lactamase with pI of 7.7. MIC determinations showed that recombinant was resistant to cefoxitin and the resistance to ceftazidime could be induced by the cefoxitin. CONCLUSION: The plasmid-mediated ampC gene cloned was identified as bla(DHA-1). IS26 observed on the flanks of the bla(DHA-1) maybe relate to the translocation of bla(DHA-1) gene region from the chromosome to plasmid.

Anti-Bacterial Agents↗

PubMedDate not supplied

[Beta-lactamases of Gram negative bacteria: never-ending clockwork!].

The acquired resistance against the wide-spectrum and highly stable beta-lactams including third-generation cephalosporins (3GC) and carbapenems is constinuously increasing and widespead with the discovery of various plasmid-encoded, or genes cassette or integrons coding for a novel beta-lactamase, always a major mechanism of resistance. To explain resistance against 3GC, with the continuing story with TEM and SHV mutated enzymes, several types of ESBL (class A) emerge the CTX-M type, at least CTX-M-40, but also other non predominant types intitled BES, GES, PLA, PER, VEB. The wider resistance including 3GC, cephamycins and beta-lactamase inhibitor is correlated to synthesis of transferable cephalosporinases (class C) usually located in the chromosome but mobilized from Enterobacter spp., Citrobacter freundii, Hafnia alvei, Morganella morganii, Aeromonas caviae. Such genes encoded the following types: ACC-1, ACT-1, CFE-1, CMY group, DHA-1, FOX group, MIR-1, MOX-1. Finally the resistance against carbapemens e.g. imipenem originally restricted to Pseudomonas aeruginosa, then to Acinetobacter baumannii and finally to enterobacteria is related to production of novel enzymes (classes B, D and A) denominated IMP, VIM SME, GIM, OXA, KPC. A striking exemple of evolution towards more and more resistance is given by Salmonella, even from animal origins, a great threat fo public health. So far it appears necessary to perform molecular approaches to identify such enzymatic production. Finally because the absence of real new drugs, the discovery of some progenitors of the gene beta-lactamase, a strict control of beta-lactam antibiotics must be provide not only in medecine or veterinary field but also in agriculture, including aquaculture for example.

Animals↗