Multiple antibiotic-resistance mechanisms including a novel combination of extended-spectrum  -lactamases in a  Klebsiella pneumoniae clinical strain isolated in Argentina

Melano, Roberto G.; Corso, Alejandra; Petroni, Alejandro; Centrón, Daniela; Orman, Betina; Pereyra, Adriana; Moreno, Noemí Alcaraz; Galas, Marcelo

doi:10.1093/jac/dkg281

Cited by 72 publications

(49 citation statements)

References 27 publications

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“…In addition, 1,043 bp of sequence downstream of bla CTX-M-2 also displays high identity to Kluyvera DNA, a finding that provides evidence that the bla CTX-M-2 gene almost certainly originates from K. ascorbata (42). It therefore seems likely that the associated ISCR1 element was involved in sequestering this section of DNA from the chromosome of K. ascorbata or a near relative into a (62), and in Morganella morganii (78). In addition, bla CTX-M2 has also been found in isolates of the gram-positive species Enterococcus faecium and serogroup G Streptococcus agalactiae (2), again in close association with ISCR1.…”

Section: Iscr1mentioning

confidence: 90%

IS CR Elements: Novel Gene-Capturing Systems of the 21st Century?

Toleman

Bennett

Walsh

2006

Microbiol Mol Biol Rev

528

481

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SUMMARY “Common regions” (CRs), such as Orf513, are being increasingly linked to mega-antibiotic-resistant regions. While their overall nucleotide sequences show little identity to other mobile elements, amino acid alignments indicate that they possess the key motifs of IS91-like elements, which have been linked to the mobility ent plasmids in pathogenic Escherichia coli. Further inspection reveals that they possess an IS91-like origin of replication and termination sites (terIS), and therefore CRs probably transpose via a rolling-circle replication mechanism. Accordingly, in this review we have renamed CRs as ISCRs to give a more accurate reflection of their functional properties. The genetic context surrounding ISCRs indicates that they can procure 5′ sequences via misreading of the cognate terIS, i.e., “unchecked transposition.” Clinically, the most worrying aspect of ISCRs is that they are increasingly being linked with more potent examples of resistance, i.e., metallo-β-lactamases in Pseudomonas aeruginosa and co-trimoxazole resistance in Stenotrophomonas maltophilia. Furthermore, if ISCR elements do move via “unchecked RC transposition,” as has been speculated for ISCR1, then this mechanism provides antibiotic resistance genes with a highly mobile genetic vehicle that could greatly exceed the effects of previously reported mobile genetic mechanisms. It has been hypothesized that bacteria will surprise us by extending their “genetic construction kit” to procure and evince additional DNA and, therefore, antibiotic resistance genes. It appears that ISCR elements have now firmly established themselves within that regimen.

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Section: Iscr1mentioning

confidence: 90%

IS CR Elements: Novel Gene-Capturing Systems of the 21st Century?

Toleman

Bennett

Walsh

2006

Microbiol Mol Biol Rev

528

481

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“…In order to prevent such an occurrence, bacteria can reduce and/or mute the expression of such porin protein channels and even modify the structure of the porin channels, reducing the permeability of these antibiotics. For example, drug resistant strains of E. coli and Enterobacter aerogenes have been shown to modify the structure of porins by narrowing the porin channel in order to reduce their permeability towards antibiotics while Klebsiella pneumoniae have been shown to reduce the expression of porins in minimizing the uptake of antibiotic molecules [36][37][38]. …”

Section: Antibiotic Efflux Pump and Reduced Permeabilitymentioning

confidence: 99%

Plant-Derived Antimicrobials: Insights into Mitigation of Antimicrobial Resistance

et al. 2018

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Antibiotic resistance had first been reported not long after the discovery of the first antibiotic and has remained a major public health issue ever since. Challenges are constantly encountered during the mitigation process of antibiotic resistance in the clinical setting; especially with the emergence of the formidable superbug, a bacteria with multiple resistance towards different antibiotics; this resulted in the term multidrug resistant (MDR) bacteria. This rapid evolution of the resistance phenomenon has propelled researchers to continuously uncover new antimicrobial agents in a bid to hopefully, downplay the rate of evolution despite a drying pipeline. Recently, there has been a paradigm shift in the mining of potential antimicrobials; in the past, targets for drug discovery were from microorganisms and at current, the focus has moved onto plants, this is mainly due to the beneficial attributes that plants are able to confer over that of microorganisms. This review will briefly discuss antibiotic resistance mechanisms employed by resistant bacteria followed by a detailed expository regarding the use of secondary metabolites from plants as a potential solution to the MDR pathogen. Finally, future prospects recommending enhancements to the usage of plant secondary metabolites to directly target antibiotic resistant pathogens will be discussed.

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“…PCR analysis followed by DNA sequencing of the amplicons was considered the standard method for characterization of ␤-lactamases. Strains were analyzed for bla NDM , bla VIM , bla IMP , bla SPM , bla KPC , bla OXA-48-like , bla SME , bla IMI/NMC-A , bla GES , bla CTX-M , bla PER , and bla CMY as described previously (16,17). Outer membrane porin profiles of non-carbapenem-susceptible, carbapenemase nonproducers were determined by SDS-PAGE (18,19).…”

Section: Bacterial Isolates (I) Isogenicmentioning

confidence: 99%

Triton Hodge Test: Improved Protocol for Modified Hodge Test for Enhanced Detection of NDM and Other Carbapenemase Producers

et al. 2016

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Accurate detection of carbapenemase-producing Gram-negative bacilli is of utmost importance for the control of nosocomial spread and the initiation of appropriate antimicrobial therapy. The modified Hodge test (MHT), a carbapenem inactivation assay, has shown poor sensitivity in detecting the worldwide spread of New Delhi metallo-␤-lactamase (NDM). Recent studies demonstrated that NDM is a lipoprotein anchored to the outer membrane in Gram-negative bacteria, unlike all other known carbapenemases. Here we report that membrane anchoring of ␤-lactamases precludes detection of carbapenemase activity by the MHT. We also show that this limitation can be overcome by the addition of Triton X-100 during the test, which allows detection of NDM. We propose an improved version of the assay, called the Triton Hodge test (THT), which allows detection of membrane-bound carbapenemases with the addition of this nonionic surfactant. This test was challenged with a panel of 185 clinical isolates (145 carrying known carbapenemase-encoding genes and 40 carbapenemase nonproducers). The THT displayed test sensitivity of >90% against NDM-producing clinical isolates, while improving performance against other carbapenemases. Ertapenem provided the highest sensitivity (97 to 100%, depending on the type of carbapenemase), followed by meropenem (92.5 to 100%). Test specificity was not affected by the addition of Triton (87.5% and 92.5% with ertapenem and meropenem, respectively). This simple inexpensive test confers a large improvement to the sensitivity of the MHT for the detection of NDM and other carbapenemases. Detection of carbapenemase producers in clinical laboratories is of major importance to define appropriate empirical antimicrobial therapy and to implement infection control measures. Acquired carbapenemases belong to three of the four known classes of ␤-lactamases, namely, Ambler class A (KPC, SME, NMC-A, IMI-1, and some allelic variants of GES), Ambler class B or metallo-␤-lactamases (MBLs) (e.g., VIM, IMP, NDM, and SPM), and Ambler class D or oxacillinases (OXAs) (e.g., OXA-48 and OXA-181) (1).The modified Hodge test (MHT) is a phenotypic screening test to identify carbapenemase producers, being recommended by the Clinical and Laboratory Standards Institute (CLSI) for Enterobacteriaceae with elevated carbapenem MICs or reduced disk diffusion inhibition zones (2). This test is based on the inactivation of a carbapenem by carbapenemase-producing strains, which enables a susceptible indicator strain to extend growth toward a disk containing this antibiotic, along the streak of inoculum of the tested strain. The MHT has shown excellent sensitivity in the detection of class A and class D carbapenemase producers (3-6). Unfortunately, the MHT performs poorly in the detection of NDM-producing isolates, with sensitivity below 50% (3-7). Because NDMs are Zn(II)-dependent enzymes, it has been suggested that the deficits of this cation in commercial media could be responsible for these false-negative results (4). Indeed, Zn(II) availabili...

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Multiple antibiotic-resistance mechanisms including a novel combination of extended-spectrum -lactamases in a Klebsiella pneumoniae clinical strain isolated in Argentina

Cited by 72 publications

References 27 publications

IS CR Elements: Novel Gene-Capturing Systems of the 21st Century?

IS CR Elements: Novel Gene-Capturing Systems of the 21st Century?

Plant-Derived Antimicrobials: Insights into Mitigation of Antimicrobial Resistance

Triton Hodge Test: Improved Protocol for Modified Hodge Test for Enhanced Detection of NDM and Other Carbapenemase Producers

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