Colistin Resistance and Extensive Genetic Variations in PmrAB and PhoPQ in Klebsiella Pneumoniae Isolates from South Korea

Cheong, Hae Suk; Kim, So Yeon; Seo, Jungyu; Wi, Yu Mi; Peck, Kyong Ran; Ko, Kwan Soo

doi:10.1007/s00284-020-02074-4

Cited by 11 publications

(5 citation statements)

References 21 publications

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“…Sequence analysis revealed amino acid variations in PmrB, PmrC, PmrE, PmrK, and MgrB compared with the colistin-susceptible K. pneumoniae reference strain, MGH78578 (Table 3). The same amino acid changes that were previously reported as contributing to colistin resistance were observed in PmrB (T246A and R256G) and PmrC (C27F, I138V, and Q319R) from the two isolates (8,30,31). Furthermore, we identified novel amino acid substitutions in PmrE (V17I, A33S, H68Q, T105A, A165E, D172N, A274G, N354D/A, E371D, and T373A) and PmrK (M114L, V117I, R372K, and G462R) from the LTH36 or LTH51 isolates, although more studies are required to prove a connection between the mutations and colistin resistance.…”

Section: Characterization Of the Colistin Resistance In The Ncp-crkp Isolates With Colistin Resistancesupporting

confidence: 82%

Molecular Characterization of Carbapenem-resistant, Colistin-resistant Klebsiella pneumoniae Isolates from a Tertiary Hospital in Jeonbuk, Korea

Lee¹,

Cho²,

Lee³

et al. 2021

jbv

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Klebsiella pneumoniae resistant to both carbapenem and colistin has become a major clinical challenge. Although such resistant isolates are rare, they have been sporadically reported from many areas of the world. To investigate the prevalence and resistant mechanisms to carbapenem-resistant, colistin-resistant K. pneumoniae among Korean patients, we selected these resistant K. pneumoniae from clinical isolates collected over a period of five years at a tertiary hospital in Jeonbuk, Korea. The minimum inhibitory concentration of a variety of antibiotics against the resistant isolates was determined by the macrodilution method or the E-test. PCR analysis was used to determine sequence types (STs) and identify the genes involved in resistance to carbapenem and colistin. In 338 K. pneumoniae clinical isolates, two exhibited both carbapenem and colistin resistance. The ST of these belonged to ST11 and ST258, the most prevalent STs with K. pneumoniae carbapenemases, but the isolates did not carry any prevalent carbapenem-hydrolyzing β-lactamase genes. The carbapenem resistance was mediated by loss of porins OmpK35 and/or OmpK36 associated with DHA-1 AmpC β-lactamase. The colistin resistance was caused by amino acid changes in PmrB, PmrC, PmrE, PmrK, and MgrB, including novel amino acid changes in PmrE and PmrK. We first reported novel carbapenem-resistant and colistin-resistant K. pneumoniae ST11 and ST258 with mutations within ompK35, ompK36, mgrB, and pmr genes in Korea. The results suggest that noncarbapenemase-producing carbapenem-resistant, colistin-resistant K. pneumoniae might be prevalent in Korea, and that better measures are necessary to control the spread of the resistant pathogen.

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Section: Characterization Of the Colistin Resistance In The Ncp-crkp Isolates With Colistin Resistancesupporting

confidence: 82%

Molecular Characterization of Carbapenem-resistant, Colistin-resistant Klebsiella pneumoniae Isolates from a Tertiary Hospital in Jeonbuk, Korea

Lee¹,

Cho²,

Lee³

et al. 2021

jbv

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“…A negative polymerase chain reaction (PCR) molecular test result cannot be used to predict colistin susceptibility because the test cannot rule out the existence of chromosomal mechanisms of resistance or even novel mcr genes not included in the test. As evidence of this limitation, high colistin resistance rates have been reported among K. pneumoniae strains that produce carbapenemase but lack mcr genes (102)(103)(104)(105). In these circumstances, a negative PCR result for mcr genes would have poor predictive value for a colistin-susceptible phenotype.…”

Section: Challenges Of Testing and Detecting Colistin Resistance Determinantsmentioning

confidence: 99%

Current Update on Intrinsic and Acquired Colistin Resistance Mechanisms in Bacteria

et al. 2021

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Colistin regained global interest as a consequence of the rising prevalence of multidrug-resistant Gram-negative Enterobacteriaceae. In parallel, colistin-resistant bacteria emerged in response to the unregulated use of this antibiotic. However, some Gram-negative species are intrinsically resistant to colistin activity, such as Neisseria meningitides, Burkholderia species, and Proteus mirabilis. Most identified colistin resistance usually involves modulation of lipid A that decreases or removes early charge-based interaction with colistin through up-regulation of multistep capsular polysaccharide expression. The membrane modifications occur by the addition of cationic phosphoethanolamine (pEtN) or 4-amino-l-arabinose on lipid A that results in decrease in the negative charge on the bacterial surface. Therefore, electrostatic interaction between polycationic colistin and lipopolysaccharide (LPS) is halted. It has been reported that these modifications on the bacterial surface occur due to overexpression of chromosomally mediated two-component system genes (PmrAB and PhoPQ) and mutation in lipid A biosynthesis genes that result in loss of the ability to produce lipid A and consequently LPS chain, thereafter recently identified variants of plasmid-borne genes (mcr-1 to mcr-10). It was hypothesized that mcr genes derived from intrinsically resistant environmental bacteria that carried chromosomal pmrC gene, a part of the pmrCAB operon, code three proteins viz. pEtN response regulator PmrA, sensor kinase protein PmrAB, and phosphotransferase PmrC. These plasmid-borne mcr genes become a serious concern as they assist in the dissemination of colistin resistance to other pathogenic bacteria. This review presents the progress of multiple strategies of colistin resistance mechanisms in bacteria, mainly focusing on surface changes of the outer membrane LPS structure and other resistance genetic determinants. New handier and versatile methods have been discussed for rapid detection of colistin resistance determinants and the latest approaches to revert colistin resistance that include the use of new drugs, drug combinations and inhibitors. Indeed, more investigations are required to identify the exact role of different colistin resistance determinants that will aid in developing new less toxic and potent drugs to treat bacterial infections. Therefore, colistin resistance should be considered a severe medical issue requiring multisectoral research with proper surveillance and suitable monitoring systems to report the dissemination rate of these resistant genes.

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“… 2019 ; Cheong et al . 2020 ). However, the parallel occurrence of mutations in MgrB, PhoPQ or PmrAB does not clarify the contribution of mutations in PmrD to the colistin resistance phenotype.…”

Section: Resistance Mechanismsmentioning

confidence: 99%

Global colistin use: a review of the emergence of resistant Enterobacterales and the impact on their genetic basis

Binsker

Käsbohrer

Hammerl

2021

FEMS Microbiology Reviews

107

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The dramatic global rise of MDR and XDR Enterobacterales in human medicine forced clinicians to the reintroduction of colistin as last-resort drug. Meanwhile, colistin is used in the veterinary medicine since its discovery leading to a steadily increasing prevalence of resistant isolates in the livestock and meat-based food sector. Consequently, transmission of resistant isolates from animals to humans, acquisition via food, and exposure to colistin in the clinic are reasons for the increased prevalence of colistin-resistant Enterobacterales in humans in the last decades. Initially, resistance mechanisms were caused by mutations in chromosomal genes. However, since the discovery in 2015, the focus has shifted exclusively to mobile colistin resistances (mcr). This review will advance the understanding of chromosomal-mediated resistance mechanisms in Enterobacterales. We provide an overview about genes involved in colistin resistance and the current global situation of colistin-resistant Enterobacterales. A comparison of the global colistin use in veterinary and human medicine highlights the effort to reduce colistin sales in veterinary medicine under the One Health approach. In contrast, it uncovers the alarming rise in colistin consumption in human medicine due to the emergence of MDR Enterobacterales, which might be an important driver for the increasing emergence of chromosome-mediated colistin resistance.

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Colistin Resistance and Extensive Genetic Variations in PmrAB and PhoPQ in Klebsiella Pneumoniae Isolates from South Korea

Cited by 11 publications

References 21 publications

Molecular Characterization of Carbapenem-resistant, Colistin-resistant Klebsiella pneumoniae Isolates from a Tertiary Hospital in Jeonbuk, Korea

Molecular Characterization of Carbapenem-resistant, Colistin-resistant Klebsiella pneumoniae Isolates from a Tertiary Hospital in Jeonbuk, Korea

Current Update on Intrinsic and Acquired Colistin Resistance Mechanisms in Bacteria

Global colistin use: a review of the emergence of resistant Enterobacterales and the impact on their genetic basis

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