Imipenem resistance in a Salmonella clinical strain due to plasmid-mediated class A carbapenemase KPC-2.
Ontology highlight
ABSTRACT:
SUBMITTER: Miriagou V
PROVIDER: S-EPMC152505 | biostudies-literature | 2003 Apr
REPOSITORIES: biostudies-literature
Publications
Imipenem resistance in a Salmonella clinical strain due to plasmid-mediated class A carbapenemase KPC-2.
Miriagou Vivi V Tzouvelekis Leonidas S LS Rossiter Shannon S Tzelepi Eva E Angulo Frederick J FJ Whichard Jean M JM
Antimicrobial agents and chemotherapy 20030401 4
A Salmonella enterica serotype Cubana isolate exhibiting resistance to most beta-lactam antibiotics, including oxyimino-cephalosporins and imipenem, was isolated from a 4-year-old boy with gastroenteritis in Maryland. beta-Lactam resistance was mediated by a conjugative plasmid that encoded KPC-2, a class A carbapenemase previously found in a Klebsiella pneumoniae isolate from the Maryland area as well. Sequence analysis of the flanking regions indicated a potential association of bla(KPC-2) wit ...[more]
Similar Datasets
Project description:The plasmid-mediated class A carbapenemase KPC-2 was isolated from unrelated Klebsiella pneumoniae isolates in Medellin, Colombia. These KPC enzymes are the first from South America and the second isolation outside of the United States. The expanding geographic spread of KPC carbapenemases underscores the importance of clinical recognition of these enzymes.
| S-EPMC1538657 | biostudies-literature
Project description:Carbapenem-resistant Enterobacteriaceae (CRE) cause health care-associated infections worldwide, and they are of severe concern due to limited treatment options. We report an outbreak of KPC-2-producing CRE that was caused by horizontal transmission of a promiscuous plasmid across different genera of bacteria and hospitals in Germany. Eleven isolates (8 Citrobacter freundii, 2 Klebsiella oxytoca, and 1 Escherichia coli) were obtained from seven critically ill patients during the six months of the outbreak in 2016. One patient developed a CRE infection while the other six patients were CRE-colonized. Three patients died in the course of the hospital stay. Six of the seven patients carried the same C. freundii clone; one K. oxytoca clone was found in two patients, and one patient carried E. coli and C. freundii. Molecular analysis confirmed the presence of a conjugative, bla KPC-2-carrying 70 kb-IncN plasmid in C. freundii and E. coli and an 80 kb-IncN plasmid in K. oxytoca. All transconjugants harbored either the 70 or 80 kb plasmid with bla KPC-2, embedded within transposon variant Tn4401g. Whole genome sequencing and downstream bioinformatics analyses of all plasmid sequences showed an almost perfect match when compared to a bla KPC-2-carrying plasmid of a large outbreak in another German hospital two years earlier. Differences in plasmid sizes and open reading frames point to the presence of inserted mobile genetic elements. There are few outbreak reports worldwide on the transmission of bla KPC-2-carrying plasmids across different bacterial genera. Our data suggest a regional and supraregional spread of bla KPC-2-carrying IncN-plasmids harboring the Tn4401g isoform in Germany.
| S-EPMC6390000 | biostudies-literature
Project description:We describe in vivo evolution of carbapenem and ceftazidime-avibactam resistance by analyzing four longitudinal Klebsiella pneumoniae clinical isolates from a patient with pneumonia following antimicrobial treatment. The patient had fever, cough associated with expectoration, and new infiltration was found on the chest CT. Antimicrobial susceptibility was determined, and whole genome sequencing (WGS) was performed to investigate its dynamic change of resistance phenotype. Population analysis profile was performed to investigate the population of Klebsiella pneumoniae. The infection started with a KPC-2-producing K. pneumoniae (ZRKP01, ceftazidime-avibactam-S/carbapenem-R). Then, after ceftazidime-avibactam treatment, the strain switched to D179Y mutant that is KPC-33 (ZRKP02, ceftazidime-avibactam-R/carbapenem-S), which restored carbapenem susceptibility. However, the restored carbapenem susceptibility in vivo was not stable and the subsequent use of imipenem against KPC-33-producing K. pneumoniae infection resulted in a reversion of KPC-2 producers (ZRKP03 and ZRKP04, ceftazidime-avibactam-S/carbapenem-R). Genetic analysis demonstrated that all four K. pneumoniae isolates belonged to sequence type 11and had identical capsular polysaccharide (KL47), identical porin genes, and same plasmid replicon types. Phylogenetic analysis indicated that four K. pneumoniae isolates showed a high degree of relatedness. Single nucleotide polymorphisms analysis indicated that the number of mutations observed in the KPC-33 isolate was more than in the wild-type KPC-2 isolates and the four KPC-Kp isolates evolved from a longitudinal evolution of K. pneumoniae harboring bla KPC-2 gene. This is the first report to observe the in vivo evolution of wild-type KPC-2 to KPC-33 and then the reversion to its original wild-type KPC-2. Through WGS, we demonstrated the role of selective pressure of antibiotic in the mutation and reversion of bla KPC genes, which leading to the dynamic change of KPC enzymes and the dynamic emergence of resistance to ceftazidime-avibactam and carbapenems. Statement: Recently, studies reported the emergence of ceftazidime-avibactam-resistant strains. The KPC mutations mediating ceftazidime-avibactam resistance are generally associated with the restoration of carbapenem susceptibility. However, clinical significance of this observation is unclear. In this manuscript, we demonstrate the role of selective pressure of antibiotic in the mutation and reversion of bla KPC genes, which leading to the dynamic change of KPC enzymes and the dynamic emergence of resistance to ceftazidime-avibactam and carbapenems. To the best of our knowledge, this is the first report to observe the in vivo evolution of wild-type KPC-2 to KPC-33 and then the reversion to its original wild-type KPC-2. It should be noted that understanding the clinical significance of this observation is of critical importance, and reversion to carbapenem susceptibility would not imply a potential role for carbapenems monotherapy. We hope our study will draw attention to clinicians, so that this agent can be used most effectively for the longest period of time.
| S-EPMC8496447 | biostudies-literature
Project description:Salmonella enterica serovar Indiana (S. Indiana) has aroused widespread concern as an important zoonotic pathogen. The molecular mechanism of multidrug resistance (MDR) in S. Indiana is not known and should be assessed. We aim to investigate the molecular mechanism of MDR and the importance of large plasmids carried class 1 integrons in the MDR of foodborne S. Indiana. Class 1 integrons in 48 S. Indiana isolates and 200 isolates of 7 other Salmonella serotypes were detected by polymerase chain reaction (PCR). To analyze the antimicrobial resistance genes (ARGs) of two S. Indiana isolates, designated S. Indiana 15 and S. Indiana 222, next-generation sequencing (NGS) was performed, and the resulting sequences were compared with the complete nucleotide sequences of S. Indiana D90 and S. Indiana C629. Comparative functional analysis was conducted between the intI1 (1,014 bp) of S. Indiana 222 and the intI1 (699 bp) of S. Indiana 15. Plasmid conjugation transfer analysis was performed to analyze the horizontal gene transfer of the integrons-related resistance genes with integron-positive and integron-negative Salmonella isolates. 64.58% of S. Indiana isolates carried class 1 integrons, which was significantly higher than that of other Salmonella serotypes (p < 0.001). The NGS results showed that the S. Indiana 15 and S. Indiana 222 isolates carried a large plasmid with a class 1 integron and multiple ARGs, similar to S. Indiana D90 and S. Indiana C629. Two integrases found in S. Indiana isolates belong to class 1 integrases and could integrate resistance genes into specific integration sites of the integrons. The conjugation frequency of intI1 (1,014 bp) was 6.08 × 10-5, which was significantly higher than that of intI1 (699 bp) (p < 0.01). The large plasmids carrying a class 1 integron and the number of ARGs were strongly correlated (p < 0.001). The conjugation frequency of integron-positive S. Indiana recipient isolates was significantly higher than that of integron-negative recipient isolates (p < 0.05). S. Indiana containing large plasmids carrying a class 1 integron more easily captured resistance genes from other bacteria (S. Enteritidis and S. Derby), which could be an important cause of the emerging pandemic of MDR clones. Graphical abstractS. Indiana containing large plasmids carrying a class 1 integron more easily captured resistance genes from other bacteria (S. Enteritidis and S. Derby), which could be an important cause of the emerging pandemic of MDR clones.
| S-EPMC9614373 | biostudies-literature
Project description:The diffusion of KPC-2 carbapenemase is closely related to the spread of Klebsiella pneumoniae of the clonal-group 258 and linked to IncFIIK plasmids. Little is known about the biology of multi-drug resistant plasmids and the reasons of their successful dissemination. Using E. coli TOP10 strain harboring a multi-replicon IncFIIK-IncFIB bla KPC-2-gene carrying plasmid pBIC1a from K. pneumoniae ST-258 clinical isolate BIC-1, we aimed to identify basal gene expression and the effects of imipenem exposure using whole transcriptome approach by RNA sequencing (RNA-Seq). Independently of the antibiotic pressure, most of the plasmid-backbone genes were expressed at low levels. The most expressed pBIC1a genes were involved in antibiotic resistance (bla KPC-2, bla TEM and aph(3')-I), in plasmid replication and conjugation, or associated to mobile elements. After antibiotic exposure, 34% of E. coli (pBIC1a) genome was differentially expressed. Induction of oxidative stress response was evidenced, with numerous upregulated genes of the SoxRS/OxyR oxydative stress regulons, the Fur regulon (for iron uptake machinery), and IscR regulon (for iron sulfur cluster synthesis). Nine genes carried by pBIC1a were up-regulated, including the murein DD-endopeptidase mepM and the copper resistance operon. Despite the presence of a carbapenemase, we observed a major impact on E. coli (pBIC1a) whole transcriptome after imipenem exposure, but no effect on the level of transcription of antimicrobial resistance genes. We describe adaptive responses of E. coli to imipenem-induced stress, and identified plasmid-encoded genes that could be involved in resistance to stressful environments.
| S-EPMC6286996 | biostudies-literature
Project description:Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-HvKP) strains have been increasingly reported, and it is important to understand the evolutionary mechanisms of these highly pathogenic and resistant bacterial pathogens. In this study, we characterized a ST11 carbapenem-resistant K. pneumoniae strain which harbored an IncFIB/IncHI1B type virulence plasmid and an IncFII/IncR type blaKPC–2-bearing plasmid. The virulence plasmid was found to be conjugative and harbored a 35-kbp fragment including aerobactin encoding cluster from virulence plasmid pLVPK and multiple resistance genes, resulting in a mosaic multi-drug resistance and virulence plasmid. This virulence plasmid could be transferred via conjugation to Escherichia coli and K. pneumoniae strains alone as well as together with the blaKPC–2-bearing plasmid. Co-transmission of virulence and blaKPC–2-bearing plasmids would directly convert a classic K. pneumoniae strain into CR-HvKP strain, leading to a sharp increase in the prevalence of CR-HvKP in clinical settings, which poses a great threat to human health.
| S-EPMC8606748 | biostudies-literature
Project description:Beta-lactamases inactivate beta-lactam antibiotics and are a major cause of antibiotic resistance. The recent outbreaks of Klebsiella pneumoniae carbapenem resistant (KPC) infections mediated by KPC type beta-lactamases are creating a serious threat to our "last resort" antibiotics, the carbapenems. KPC beta-lactamases are serine carbapenemases and are a subclass of class A beta-lactamases that have evolved to efficiently hydrolyze carbapenems and cephamycins which contain substitutions at the alpha-position proximal to the carbonyl group that normally render these beta-lactams resistant to hydrolysis. To investigate the molecular basis of this carbapenemase activity, we have determined the structure of KPC-2 at 1.85 A resolution. The active site of KPC-2 reveals the presence of a bicine buffer molecule which interacts via its carboxyl group with conserved active site residues S130, K234, T235, and T237; these likely resemble the interactions the beta-lactam carboxyl moiety makes in the Michaelis-Menten complex. Comparison of the KPC-2 structure with non-carbapenemases and previously determined NMC-A and SME-1 carbapenemase structures shows several active site alterations that are unique among carbapenemases. An outward shift of the catalytic S70 residue renders the active sites of the carbapenemases more shallow, likely allowing easier access of the bulkier substrates. Further space for the alpha-substituents is potentially provided by shifts in N132 and N170 in addition to concerted movements in the postulated carboxyl binding pocket that might allow the substrates to bind at a slightly different angle to accommodate these alpha-substituents. The structure of KPC-2 provides key insights into the carbapenemase activity of emerging class A beta-lactamases.
| S-EPMC2596071 | biostudies-literature
Project description:KPC-50 is a KPC-3 variant identified from a Klebsiella pneumoniae clinical isolate recovered in Switzerland in 2019. Compared to KPC-3, KPC-50 shows (i) a three-amino-acid insertion (Glu-Ala-Val) between amino acids 276 and 277, (ii) an increased affinity to ceftazidime, (iii) a decreased sensitivity to avibactam, explaining the ceftazidime-avibactam resistance, and (iv) an association with a sharp reduction of its carbapenemase activity.
| S-EPMC7526841 | biostudies-literature
Project description:A novel mcr variant, named mcr-1.2, encoding a Gln3-to-Leu functional variant of MCR-1, was detected in a KPC-3-producing ST512 Klebsiella pneumoniae isolate collected in Italy from a surveillance rectal swab from a leukemic child. The mcr-1.2 gene was carried on a transferable IncX4 plasmid whose structure was very similar to that of mcr-1-bearing plasmids previously found in Escherichia coli and K. pneumoniae strains from geographically distant sites (Estonia, China, and South Africa).
| S-EPMC4997870 | biostudies-literature
Project description:BACKGROUND:Salmonella infection poses significant public health threat globally, especially in resource-limited countries. Emergence and spread of antibiotic resistant strains to fluoroquinolones have led to treatment failures and increased mortality in Salmonella infection. However, there is dearth of information regarding mechanisms of resistance to fluoroquinolones in Ghana. This study therefore sought to identify chromosomal mutations and plasmid-mediated resistance as possible mechanisms of fluoroquinolone resistance from clinical isolates in Ghana. METHODS:This was a retrospective study of archived isolates biobanked at Kumasi Centre for Collaborative Research in Tropical Medicine, Ghana. Isolates were obtained from blood, stool and oropharynx samples at two hospitals, between May, 2016 and January, 2018. Salmonella identification was done using standard microbiological protocols and antibiotic susceptibility testing performed by Kirby-Bauer disc diffusion method. Isolates with intermediate susceptibility and/or resistance to nalidixic acid and/or ciprofloxacin were selected and examined for chromosomal mutations by Sanger sequencing and plasmid-mediated resistance by PCR. RESULTS:Of 133 biobanked isolates cultured, 68 (51.1%) and 16 (12%) were identified as Salmonella Typhi and non-typhoidal Salmonella (NTS), respectively. Sequence analysis of gyrA gene revealed the presence of 5 different nonsynonymous mutations, with the most frequent mutation (Ile203Ser) occurring in 12 out of 13 isolates tested. Gyrase B (gyrB) gene had 1 nonsynonymous mutation in 3 out of 13 isolates, substituting phenylalanine with leucine at codon 601 (Phe601Leu). No mutation was observed in parC and parE genes. Two NTS isolates were found to harbour qnrS plasmid-mediated resistant gene of molecular size 550?bp with high ciprofloxacin MIC of 0.5??g/ml. CONCLUSION:This study reports for the first time in Ghana plasmid-mediated fluoroquinolone resistant gene qnrS in Salmonella clinical isolates. Nonsynonymous mutations of gyrA and gyrB genes likely to confer Salmonella reduced susceptibility to ciprofloxacin were also reported.
| S-EPMC6819380 | biostudies-literature