Carbapenem Resistance Mechanisms in Pseudomonas aeruginosa Clinical Isolates

ABSTRACT In order to define the contributions of the mechanisms for carbapenem resistance in clinical strains of Pseudomonas aeruginosa, we investigated the presence of OprD, the expressions of the MexAB-OprM and MexEF-OprN systems, and the production of the β-lactamases for 44 clinical strains. All of the carbapenem-resistant isolates showed the loss of or decreased levels of OprD. Three strains overexpressed the MexAB-OprM efflux system by carrying mutations inmexR. These three strains had the amino acid substitution in MexR protein, Arg (CGG) → Gln (CAG), at the position of amino acid 70. None of the isolates, however, expressed the MexEF-OprN efflux system. For the characterization of β-lactamases, at least 13 isolates were the depressed mutants, and 12 strains produced secondary β-lactamases. Based on the above resistance mechanisms, the MICs of carbapenem for the isolates were analyzed. The MICs of carbapenem were mostly determined by the expression of OprD. The MICs of meropenem were two- to four-fold increased for the isolates which overexpressed MexAB-OprM in the background of OprD loss. However, the elevated MICs of meropenem for some individual isolates could not be explained. These findings suggested that other resistance mechanisms would play a role in meropenem resistance in clinical isolates of P. aeruginosa.

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Characterization of resistance mechanisms of Enterobacter cloacae Complex co-resistant to carbapenem and colistin

BMC Microbiology ◽

10.1186/s12866-021-02250-x ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Shixing Liu ◽

Renchi Fang ◽

Ying Zhang ◽

Lijiang Chen ◽

Na Huang ◽

...

Keyword(s):

Lipid A ◽

Efflux Pump ◽

Resistance Mechanism ◽

Carbapenem Resistance ◽

Enterobacter Cloacae ◽

Resistance Mechanisms ◽

Colistin Resistance ◽

Carbapenem Resistant ◽

Horizontal Spread

Abstract Background The emergence of carbapenem-resistant and colistin-resistant ECC pose a huge challenge to infection control. The purpose of this study was to clarify the mechanism of the carbapenems and colistin co-resistance in Enterobacter cloacae Complex (ECC) strains. Results This study showed that the mechanisms of carbapenem resistance in this study are: 1. Generating carbapenemase (7 of 19); 2. The production of AmpC or ESBLs combined with decreased expression of out membrane protein (12 of 19). hsp60 sequence analysis suggested 10 of 19 the strains belong to colistin hetero-resistant clusters and the mechanism of colistin resistance is increasing expression of acrA in the efflux pump AcrAB-TolC alone (18 of 19) or accompanied by a decrease of affinity between colistin and outer membrane caused by the modification of lipid A (14 of 19). Moreover, an ECC strain co-harboring plasmid-mediated mcr-4.3 and blaNDM-1 has been found. Conclusions This study suggested that there is no overlap between the resistance mechanism of co-resistant ECC strains to carbapenem and colistin. However, the emergence of strain co-harboring plasmid-mediated resistance genes indicated that ECC is a potential carrier for the horizontal spread of carbapenems and colistin resistance.

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Diversity of TEM Mutants in Proteus mirabilis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.43.11.2671 ◽

1999 ◽

Vol 43 (11) ◽

pp. 2671-2677 ◽

Cited By ~ 51

Author(s):

R. Bonnet ◽

C. De Champs ◽

D. Sirot ◽

C. Chanal ◽

R. Labia ◽

...

Keyword(s):

Amino Acid ◽

Amino Acid Substitution ◽

Proteus Mirabilis ◽

Clinical Isolates ◽

Amino Acid Substitutions ◽

First Report ◽

Conjugative Plasmids ◽

Extended Spectrum ◽

Nucleotide Mutation

ABSTRACT In a survey of resistance to amoxicillin among clinical isolates ofProteus mirabilis, 10 TEM-type β-lactamases were characterized: (i) the well-known penicillinases TEM-1 and TEM-2, the extended-spectrum β-lactamases (ESBLs) TEM-3 and TEM-24, and the inhibitor-resistant TEM (IRT) TEM-44 and (ii) five novel enzymes, a penicillinase TEM-57 similar to TEM-1, an ESBL TEM-66 similar to TEM-3, and three IRTs, TEM-65, TEM-73, and TEM-74. The penicillinase TEM-57 and the ESBL TEM-66 differed from TEM-1 and TEM-3, respectively, by the amino acid substitution Gly-92→Asp (nucleotide mutation G-477→A). This substitution could have accounted for the decrease in pIs (5.2 for TEM-57 and 6.0 for TEM-66) but did not necessarily affect the intrinsic activities of these enzymes. The IRT TEM-65 was an IRT-1-like IRT (Cys-244) related to TEM-2 (Lys-39). The two other IRTs, TEM-73 and TEM-74, were related to IRT-1 (Cys-244) and IRT-2 (Ser-244), respectively, and harbored the amino acid substitutions Leu-21→Phe and Thr-265→Met. In this study, the ESBLs TEM-66, TEM-24, and TEM-3 were encoded by large (170- to 180-kb) conjugative plasmids that exhibited similar patterns after digestion and hybridization with the TEM and AAC(6′)I probes. The three IRTs TEM-65, TEM-73, and TEM-74 were encoded by plasmids that ranged in size from 42 to 70 kb but for which no transfer was obtained. The characterization of five new plasmid-mediated TEM-type β-lactamases and the first report of TEM-24 in P. mirabilis are evidence of the wide diversity of β-lactamases produced in this species and of its possible role as a β-lactamase-encoding plasmid reservoir.

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Distribution of carbapenem resistance mechanisms in clinical isolates of XDR Pseudomonas aeruginosa

European Journal of Clinical Microbiology & Infectious Diseases ◽

10.1007/s10096-019-03585-0 ◽

2019 ◽

Vol 38 (8) ◽

pp. 1547-1552 ◽

Cited By ~ 6

Author(s):

Annalisa De Rosa ◽

Nico T. Mutters ◽

Claudio M. Mastroianni ◽

Stefan J. Kaiser ◽

Frank Günther

Keyword(s):

Pseudomonas Aeruginosa ◽

Carbapenem Resistance ◽

Resistance Mechanisms ◽

Clinical Isolates

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Problematic clinical isolates of Pseudomonas aeruginosa from the university hospitals in Sofia, Bulgaria: current status of antimicrobial resistance and prevailing resistance mechanisms

Journal of Medical Microbiology ◽

10.1099/jmm.0.46986-0 ◽

2007 ◽

Vol 56 (7) ◽

pp. 956-963 ◽

Cited By ~ 17

Author(s):

Tanya Strateva ◽

Vessela Ouzounova-Raykova ◽

Boyka Markova ◽

Albena Todorova ◽

Yulia Marteva-Proevska ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Antimicrobial Agents ◽

Carbapenem Resistance ◽

Multidrug Resistant ◽

Resistance Mechanisms ◽

Clinical Isolates ◽

Current Status ◽

University Hospitals ◽

Active Efflux ◽

Genes Encoding

A total of 203 clinical isolates of Pseudomonas aeruginosa was collected during 2001–2006 from five university hospitals in Sofia, Bulgaria, to assess the current levels of antimicrobial susceptibility and to evaluate resistance mechanisms to antipseudomonal antimicrobial agents. The antibiotic resistance rates against the following antimicrobials were: carbenicillin 93.1 %, azlocillin 91.6 %, piperacillin 86.2 %, piperacillin/tazobactam 56.8 %, ceftazidime 45.8 %, cefepime 48.9 %, cefpirome 58.2 %, aztreonam 49.8 %, imipenem 42.3 %, meropenem 45.5 %, amikacin 59.1 %, gentamicin 79.7 %, tobramycin 89.6 %, netilmicin 69.6 % and ciprofloxacin 80.3 %. A total of 101 of the studied P. aeruginosa isolates (49.8 %) were multidrug resistant. Structural genes encoding class A and class D β-lactamases showed the following frequencies: bla VEB-1 33.1 %, bla PSE-1 22.5 %, bla PER-1 0 %, bla OXA-groupI 41.3 % and bla OXA-groupII 8.8 %. IMP- and VIM-type carbapenemases were not detected. In conclusion, the studied clinical strains of P. aeruginosa were problematic nosocomial pathogens. VEB-1 extended-spectrum β-lactamases appear to have a significant presence among clinical P. aeruginosa isolates from Sofia. Carbapenem resistance was related to non-enzymic mechanisms such as a deficiency of OprD proteins and active efflux.

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Characterization of saccharolytic nonfermentative bacteria associated with man

Canadian Journal of Microbiology ◽

10.1139/m70-062 ◽

1970 ◽

Vol 16 (5) ◽

pp. 351-362 ◽

Cited By ~ 27

Author(s):

M. J. Pickett ◽

Margaret M. Pedersen

Keyword(s):

Pseudomonas Aeruginosa ◽

Pseudomonas Putida ◽

Pseudomonas Fluorescens ◽

Pseudomonas Stutzeri ◽

Clinical Isolates ◽

Gram Negative ◽

Clinical Strains ◽

Pseudomonas Maltophilia ◽

Reference Strains

Features of 378 clinical isolates of saccharolytic, nonfermentative Gram-negative rods and 20 reference strains were examined. All but four of the clinical strains were assigned to recognized taxa, namely Acinetobacter, Chromobacterium, Flavobacterium, Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas maltophilia, Pseudomonas multivorans, Pseudomonas putida, Pseudomonas stutzeri, and Xanthomonas.

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P867 Carbapenem resistance mechanisms in Norwegian clinical isolates of Pseudomonas aeruginosa

International Journal of Antimicrobial Agents ◽

10.1016/s0924-8579(07)70708-2 ◽

2007 ◽

Vol 29 ◽

pp. S223-S224

Author(s):

Ø. Samuelsen ◽

L. Buarø ◽

B. Aasnæs ◽

C.G. Giske ◽

B. Haldorsen ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Carbapenem Resistance ◽

Resistance Mechanisms ◽

Clinical Isolates

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Mutations in PA3574 (nalD) Lead to Increased MexAB-OprM Expression and Multidrug Resistance in Laboratory and Clinical Isolates of Pseudomonas aeruginosa

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.49.5.1782-1786.2005 ◽

2005 ◽

Vol 49 (5) ◽

pp. 1782-1786 ◽

Cited By ~ 74

Author(s):

Mara L. Sobel ◽

Didier Hocquet ◽

Lily Cao ◽

Patrick Plesiat ◽

Keith Poole

Keyword(s):

Pseudomonas Aeruginosa ◽

Multidrug Resistance ◽

Resistant Mutant ◽

Multidrug Resistant ◽

Clinical Isolates ◽

Multidrug Efflux ◽

Efflux System ◽

Clinical Strains ◽

Transposon Insertion ◽

Multidrug Efflux System

ABSTRACT Mutations in genes mexR and nalC have previously been shown to drive overexpression of the MexAB-OprM multidrug efflux system in Pseudomonas aeruginosa. A transposon insertion multidrug-resistant mutant of P. aeruginosa overproducing MexAB-OprM was disrupted in yet a third gene, PA3574, encoding a probable repressor of the TetR/AcrR family that we have dubbed NalD. Clinical strains overexpressing MexAB-OprM but lacking mutations in mexR or nalC were also shown to carry mutations in nalD. Moreover, the cloned nalD gene reduced the multidrug resistance and MexAB-OprM expression of the transposon mutant and clinical isolates, highlighting the significance of the nalD mutations vis-à-vis MexAB-OprM overexpression in these isolates.

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New Delhi Metallo-β-lactamase (NDM)-mediated Carbapenem-Resistant Pseudomonas aeruginosa Clinical Isolates in Sudan

South Asian Journal of Research in Microbiology ◽

10.9734/sajrm/2018/v1i3775 ◽

2018 ◽

pp. 1-5

Author(s):

Salma Elnour Rahma Mohamed ◽

Alfadil Alobied ◽

Mohamed Ibrahim Saeed ◽

Wafa Mohamed Hussien

Keyword(s):

Pseudomonas Aeruginosa ◽

Teaching Hospital ◽

Carbapenem Resistance ◽

Clinical Isolates ◽

Diffusion Method ◽

New Delhi ◽

Army Hospital ◽

Carbapenem Resistant ◽

Wide Range ◽

Data Documentation

Carbapenem resistance mediated by NDM is particularly gruesome as this carbapenemase can hydrolyze a wide range of β-lactam antibiotics. Aim: This study aims to detect NDM mediated carbapenem resistance in clinical isolates of Pseudomonas aeruginosa. Materials and Methods: 50 multi-drug resistant clinical urinary isolates of Pseudomonas aeruginosa from three major hospitals in Khartoum state Sudan; Khartoum Teaching Hospital, Medical Army Hospital and Omdurman teaching hospital, in period from July 2016 to September 2017, were investigated for carbapenem resistance using standard disc diffusion method and underwent real-time PCR to detect carbapenem resistance gene blaNDM. Data were analyzed using IBM SPSS. Results: 60% were positive for the blaNDM, 82% were resistant to Imipenem and 75% of the samples were resistant to Meropenem. Conclusion: The emergence of carbapenem resistance is a global problem that requires earnest attention. To make the suitable preventive measures, the emergence of these genes must be monitored closely. Our findings revealed that carbapenem-resistant due to the gene blaNDM is accounted for 60% of the cases, and due to lack of proper data documentation about the emergence of this gene in Sudan, these cases to the best of our knowledge are the first to be reported in Sudan.

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