Molecular characterization of carbapenem-resistant <i>Klebsiella pneumoniae</i> isolates with focus on antimicrobial resistance

Yu, Xiaoling; Zhang, Wen; Zhao, Zhiping; Ye, Chengsong; Zhou, Shao-Lai; Wu, Shaogui; Han, Lijing; Han, Zhaofang; Ye, Hanhui

doi:10.1101/778795

Cited by 6 publications

(7 citation statements)

References 38 publications

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“…The coexistence of carbapenemase and ESBL was found in 18 isolates. The high incidence (67%) of isolates with coexpression of carbapenemase and ESBL found in this study has also been noted in previous studies from Tunisia and other parts of the world (Uz Zaman et al 2014;Loucif et al 2016;Yu et al 2019;Messaoudi et al 2020;Sharahi et al 2021).…”

Section: Phenotypic and Genotypic Profiles Of Carbapenemresistant Iso...supporting

confidence: 89%

Co-occurrence of genes encoding carbapenemase, ESBL, pAmpC and non-β-Lactam resistance among Klebsiella pneumonia and E. coli clinical isolates in Tunisia

Sallem

Laribi

Arfaoui

et al. 2022

Letters in Applied Microbiology

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This study aimed to investigate the molecular mechanisms of carbapenem and colistin resistance in K. pneumoniae and E. coli isolates obtained from hospitalized patients in Carthagene International Hospital of Tunis. A total of 25 K. pneumoniae and 2 E. coli clinical isolates with reduced susceptibility to carbapenems were recovered. Susceptibility testing and phenotypic screening tests were carried out. ESBL, AmpC, carbapenemase and other antibiotic resistance genes were sought by PCR‐sequencing. The presence of plasmid‐mediated colistin resistance genes (mcr‐1‐8) was examined by PCR and the nucleotide sequence of the mgrB gene was determined. The analysis of plasmid content was performed by PCR‐Based Replicon Typing (PBRT). The clonality of isolates was assessed by PFGE and multilocus sequence typing (MLST). All of the isolates produced carbapenemase activity. They showed a great variation in the distribution of ESBL, AmpC, carbapenemase and other plasmid‐mediated resistance determinants. K. pneumoniae isolates carried blaNDM‐1 (n = 11), blaOXA‐48 (n = 11), blaNDM‐1 + blaOXA‐48 (n = 1), blaNDM‐1 + blaVIM‐1 (n = 1), blaOXA‐204 (n = 1), along with blaCTX‐M, blaOXA, blaTEM, blaCMY, blaDHA and blaSHV genes variants on conjugative plasmid of IncL/M, IncR, IncFIIK, IncFIB, and IncHI1 types. Three sequence types ST101, ST307 and ST15 were identified. The mgrB alteration g109a (G37S) was detected in a single colistin‐resistant, NDM‐1 and OXA‐48‐coproducing K. pneumoniae isolate. The two E. coli isolates belonged to ST95, co‐produced NDM‐1 and CTX‐M‐15, and harboured plasmid of IncFII and IncFIB types. To our knowledge, this is the first report in Tunisia of NDM‐1, OXA‐48, and CTX‐M‐15 coexistence in colistin‐resistant K. pneumoniae ST15.

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Section: Phenotypic and Genotypic Profiles Of Carbapenemresistant Iso...supporting

confidence: 89%

Co-occurrence of genes encoding carbapenemase, ESBL, pAmpC and non-β-Lactam resistance among Klebsiella pneumonia and E. coli clinical isolates in Tunisia

Sallem

Laribi

Arfaoui

et al. 2022

Letters in Applied Microbiology

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“…We also found that all ST15 CRKP isolates carried the gene oqxAB encoding the quinolone efflux pump and the phosphomycin resistance gene fosA [14]. According to previous studies, oqxAB encodes the efflux pump responsible for quinolone resistance, but it cannot be excluded that cephalosporins, carbapenems, and other antibiotics are pumped from the K. pneumoniae cell membrane through this efflux pump [15], while fosA may be widespread in gram-negative bacteria, which is consistent with previous studies [16]. Also tetracycline resistance gene tet(A) (92%), aminoglycoside resistance genes aac(3)-lid (100%) and aac(6')-lb-cr (69%).…”

Section: Antibiotic Resistance Genes (Args)mentioning

confidence: 71%

Epidemiology of carbapenem-resistant Klebsiella pneumoniae ST15 of producing KPC-2, SHV-106 and CTX-M-15 in Anhui, China

Zhao

et al. 2022

BMC Microbiol

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Background: It is well known that carbapenem-resistant Klebsiella pneumoniae (CRKP) has become a more problematic public health issue due to its widespread spread worldwide. In China, ST11-type CRKP is the most prevalent CRKP, but ST15-type CRKP, a recently prevalent high-risk clone, has emerged widely throughout China, posing a serious public health risk. Therefore, we conducted an epidemiological of an outbreak of ST15 CRKP of producing CTX-M-15, KPC-2 and SHV-106 in a tertiary hospital in Anhui, China, to Understanding the potential risks of the current STT15 CRKP outbreak. Results: From July 2021 to December 2021, 13 ST15 CRKP isolates were identified by collecting non-repeated clinical multidrug-resistant isolates, with all capsular typing of serotype KL19. All ST15 CRKP isolates were resistant to cephalosporins, carbapenems and quinolones, but were sensitive to amikacin, tigecycline and polymyxin B. In addition, isolates carried blaSHV−106 (100%), blaKPC−2 (69%), blaCTX−M−15 (69%), blaTEM−1B (69%), blaOXA−1 (62%) and blaLAP−2 (8%), as well as iron chelators (iutA, ybt, fyuA, ent, fepA, irp1, irp2, 100%) were detected. In phenotyping experiments, all ST15 CRKP exhibited lower growth rates than NTUH-K2044, and all ST15 CRKP did not exhibit mucoviscositty characteristics. However, in the Galleria mellonella infection model, isolates 21081212, 21081241 and 21091216 were more lethal than the hypervirulent isolates NTUH-K2044. Sequencing results showed that the genetic environment surrounding the genes blaSHV−106, blaKPC−2, blaCTX−M−15, blaOXA−1 and blaTEM−1B were all identical in the ST15 CRKP isolates. Phylogenetic analysis showed that 13 ST15 CRKP isolates were divided into three subgroups, and when placed in global analysis, 10 of them were highly homologous to isolates from Jiangsu, two were highly homologous to isolates from Zhejiang, and one was homologous to an isolate from an unlabelled region. Conclusion: Our research shows that ST15 CRKP, which carries multiple β-lactamases genes and siderophores-encoding genes, may be evolving to hypervirulence and may have spread widely in localised areas. Therefore, environmental surveillance and clinical infection control in hospitals should be strengthened to prevent further spread of ST15 CRKP.

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“…1a, b. A rational design approach has been applied to the putative Komodo dragon cathelicidin sequences in order to generate a series of novel synthetic peptide derivatives(Table 1).Carbapenem-resistant Klebsiella pneumonia (CRKP) is often highly resistant to multiple antibiotics including all betalactams, fluoroquinolones and aminoglycosides[35]. To investigate the ability of a library of novel, synthetic antimicrobial peptides against carbapenem-resistant Klebsiella pneumonia, we performed MIC assays according to CLSI standards.…”

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confidence: 99%

Komodo-dragon cathelicidin-inspired peptides are antibacterial against carbapenem-resistant Klebsiella pneumoniae

Hitt

Bishop

Hoek

2020

Journal of Medical Microbiology

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Introduction. The rise of carbapenem-resistant enterobacteriaceae (CRE) is a growing crisis that requires development of novel therapeutics. Hypothesis. To this end, cationic antimicrobial peptides (CAMPs) represent a possible source of new potential therapeutics to treat difficult pathogens such as carbapenem-resistant Klebsiella pneumoniae (CRKP), which has gained resistance to many if not all currently approved antibiotics, making treatment difficult. Aim. To examine the anti-CRKP antimicrobial activity of the predicted cathelicidins derived from Varanus komodoensis (Komodo dragon) as well as synthetic antimicrobial peptides that we created. Methodology. We determined the minimum inhibitory concentrations of the peptides against CRKP. We also characterized the abilities of these peptides to disrupt the hyperpolarization of the bacterial membrane as well as their ability to form pores in the membrane. Results. We did not observe significant anti-CRKP activity for the predicted native Komodo cathelicidin peptides. We found that the novel peptides DRGN-6,-7 and -8 displayed significant antimicrobial activity against CRKP with MICs of 4–8 µg ml−1. DRGN-6 peptide was the most effective peptide against CRKP. Unfortunately, these peptides showed higher than desired levels of hemolysis, although in vivo testing in the waxworm Galleria mellonella showed no mortality associated with treatment by the peptide; however, CRKP-infected waxworms treated with peptide did not show an improvement in survival. Conclusion. Given the challenges of treating CRKP, identification of peptides with activity against it represents a promising avenue for further research. Given DRGN-6′s similar level of activity to colistin, DRGN-6 is a promising template for the development of novel antimicrobial peptide-based therapeutics.

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Molecular characterization of carbapenem-resistant Klebsiella pneumoniae isolates with focus on antimicrobial resistance

Cited by 6 publications

References 38 publications

Co-occurrence of genes encoding carbapenemase, ESBL, pAmpC and non-β-Lactam resistance among Klebsiella pneumonia and E. coli clinical isolates in Tunisia

Co-occurrence of genes encoding carbapenemase, ESBL, pAmpC and non-β-Lactam resistance among Klebsiella pneumonia and E. coli clinical isolates in Tunisia

Epidemiology of carbapenem-resistant Klebsiella pneumoniae ST15 of producing KPC-2, SHV-106 and CTX-M-15 in Anhui, China

Komodo-dragon cathelicidin-inspired peptides are antibacterial against carbapenem-resistant Klebsiella pneumoniae

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