Colistin-Resistant Klebsiella pneumoniae: Prevalence of Integrons and Synergistic Out Turn for Colistin-Meropenem

Manohar, Prasanth; Shanthini, Thamaraiselvan; Pandey, Ekta; Mahesan, J B; Gothandam, Kodiveri Muthukaliannan; Bozdoğan, Bülent; Nachimuthu, Ramesh

doi:10.5812/archcid.55099

Cited by 3 publications

(6 citation statements)

References 30 publications

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“…It would be highly dangerous as it might be challenging to curb the spread if not taken properly measures and impede antibiotic therapy. 28 Also, it agrees with another report, which showed that the availability of class 1 integron in the MDR strains could have an impact on the dispersal of clustered resistance genes. 35 The detection of hypermucoviscous (HMV) phenotype is feasible and can be easily performed in any microbiology laboratory.…”

Section: Discussionsupporting

confidence: 90%

“…But mcr (1-5) genes were not detected, which shows a lack of plasmid-mediated resistance, which is similar to our previous report. 28 The colistin resistance could be due to chromosomal-mediated such as alteration in the LPS target, high mucous production, or biofilm formation. 29 Through genome sequencing, no unique alternations were identified in colistin-resistant isolates.…”

Section: Discussionmentioning

confidence: 99%

“…In certain strains, the resistance was due to chromosomal-mediated; namely, mgrB inactivation, alteration, or upregulation in the two-component regulatory system, and in some cases, the resistance was due to the active efflux pumps. 28,30 All the K. pneumoniae isolates used in this study were sensitive to tigecycline. It supports the rare occurrence of tigecycline resistance in our regions and the earlier study where the tigecycline resistance in K. pneumoniae was found to be lesser than in other antibiotics.…”

Section: Discussionmentioning

confidence: 99%

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Detection of HypervirulentKlebsiella pneumoniaefrom Clinical Samples in Tamil Nadu

Shanthini

Manohar

Hua

et al. 2023

Preprint

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Klebsiella pneumoniae is one of the significant opportunistic pathogens which cause both nosocomial and community-acquired infections. This study focuses on the molecular characterization of hypervirulent K. pneumoniae isolated from clinical samples in Tamil Nadu. A total of 30 clinical K. pneumoniae isolates were collected from the diagnostic centres located in Trichy, Madurai, and Chennai. On subjected to the antibiotic susceptibility testing, it was found that 73% were multi-drug resistant. The string test showed that 46.6% of the isolates were hypermucoviscous (HMV). Molecular studies revealed the absence of mcr (1-5) genes. The isolates belonging to capsular types K1 (n=5), K2 (n=6) and K5 (n=2) were detected. Virulence genes namely rmpA (n=5), aerobactin (n=8), and KfuBC (n=8) were identified using multiplex polymerase chain reaction. Through molecular studies, 22 isolates were found to be classical K. pneumoniae (cKP) and 8 were hypervirulent K. pneumoniae (hvKP). The genome sequencing of five isolates revealed that the strains belong to ST86 and ST23. In vivo studies using Galleria mellonella showed that HMV-hvKP strains were highly pathogenic among the hvKP strains and the non-K1/K2 and K2 strains were pathogenic among the cKP strains. Our data revealed the emergence of colistin-resistant hvKP strains in Tamil Nadu, India.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Detection of HypervirulentKlebsiella pneumoniaefrom Clinical Samples in Tamil Nadu

Shanthini

Manohar

Hua

et al. 2023

Preprint

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“…Interestingly, the combination of two last-resort antibiotics, colistin and meropenem, showed a synergistic effect against four MDR K. pneumoniae. Although earlier studies showed synergy of the colistin-meropenem combination [28], this is one of the first against the clinical isolates collected from Mizoram. These results again support the combinational activity of two antibiotics against resistant bacterial pathogens.…”

Section: Discussionmentioning

confidence: 84%

The Emergence of Carbapenem-Resistant Gram-Negative Bacteria in Mizoram, Northeast India

Vanlalruati¹,

Loganathan

Manohar

et al. 2022

Microbiology Research

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(Background) Numerous reports on carbapenem resistance in different parts of India have been published, yet there are insufficient studies on the prevalence of antibiotic resistance in the northeast region of the country. This study evaluated the emergence of carbapenem resistance in the clinical isolates collected in Mizoram. (Results) A total of 141 Gram-negative clinical isolates were collected from the two hospitals, including the Civil Hospital in Lunglei and the Synod Hospital in Aizawl. The isolates include Escherichia coli (n = 62, 43.9%), Klebsiella spp. (n = 43, 30.4%), Pseudomonas aeruginosa (n = 9, 6.3%), Serratia marcescens (n = 3, 2.1%), Proteus mirabilis (n = 2, 1.4%), Shigella spp. (n = 4, 2.8%), Enterobacter spp. (n = 6, 4.2%) and Acinetobacter spp. (n = 12, 8.5%). The isolates were found to be resistant to meropenem (11%), colistin (48%), tigecycline (25%) and cefotaxime (50%). A total of four E. coli and one Shigella sonnei encoded the blaOXA-48-like gene. The blaCTX-M-1 gene was detected in 13 isolates, of which eight were E. coli, two Shigella flexneri, and one isolates each of K. pneumoniae, K. oxytoca and Shigella sonnei, respectively. (Conclusion) Carbapenem-resistant Enterobacteriaceae are common among other parts of India, despite limited access to antibiotics, the emergence of resistance in the northeastern region is worrying.

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“…Interestingly, there have been other reports showing colistin-resistant isolates not harbouring mcr genes. In the study by Manohar et al, 24 colistin-resistant Klebsiella pneumoniae isolates were investigated and none of them carried mcr-1 or mcr-2 [37]. Potentially, this could be due to the loss of LPS as recently shown by mutations in lipid A biosynthesis genes in E. coli [38].…”

Section: Plos Onementioning

confidence: 99%

Rough-type and loss of the LPS due to lpx genes deletions are associated with colistin resistance in multidrug-resistant clinical Escherichia coli isolates not harbouring mcr genes

et al. 2020

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The emergence of multidrug-resistant Escherichia coli has become a great challenge in treating nosocomial infections. The polymyxin antibiotic colistin is used as a 'last-line' therapy for such strains, but resistance to colistin is increasingly emerging all over the world. In this study, we investigated lipopolysaccharides (LPS) of colistin-resistant isolates and examined mutations in lpx genes in strains not harbouring mcr genes. We examined 351 clinical E. coli isolates with 38 showing reduced susceptibility to colistin. These isolates were collected from different clinical specimens including blood, urine, and wounds, but no stool. After confirmation of the isolates via a BD Phoenix-100 system (Becton Dickinson, USA), we performed antimicrobial susceptibility tests to characterize the resistance pattern of these isolates to different classes of antibiotics, using the disk diffusion test. The Minimum Inhibitory Concentration (MIC) of colistin was determined using E-test strips. The presence of mobile colistin resistance (mcr-1 and mcr-2) genes was tested for all isolates. LPS (including lipid A) were extracted from all isolates and associated lpx genes analyzed by PCR and sequencing. Among the 38 clinical E. coli isolates with reduced susceptibility to colistin, 52% were resistant to colistin. The MICs of colistin ranged from 0.5 μg/ml to >256 μg/ml. Within the 20 colistin-resistant strains, six isolates carried the mcr-1 gene, but not mcr-2. Heterologous expression of the mcr-1 gene in susceptible E. coli DH5α increased the MIC of colistin by eight-fold. The remaining 14 isolates, were negative for both mcr genes. Six isolates were further negative for LPS production and five showed rough LPS phenotypes. Here we present evidence that loss of LPS or lipid A-deficiency can lead to colistin-resistance in clinical E. coli isolates not harbouring mcr genes.

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Colistin-Resistant Klebsiella pneumoniae: Prevalence of Integrons and Synergistic Out Turn for Colistin-Meropenem

Cited by 3 publications

References 30 publications

Detection of HypervirulentKlebsiella pneumoniaefrom Clinical Samples in Tamil Nadu

Detection of HypervirulentKlebsiella pneumoniaefrom Clinical Samples in Tamil Nadu

The Emergence of Carbapenem-Resistant Gram-Negative Bacteria in Mizoram, Northeast India

Rough-type and loss of the LPS due to lpx genes deletions are associated with colistin resistance in multidrug-resistant clinical Escherichia coli isolates not harbouring mcr genes

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