Genetic Diversity of Polymyxin-Resistance Mechanisms in Clinical Isolates of Carbapenem-Resistant Klebsiella pneumoniae: a Multicenter Study in China

Li, Ziyao; Liu, Xinmeng; Lei, Zichen; Li, Chen; Zhang, Feilong; Wu, Yongli; Yang, Xinrui; Zhao, Jun; Zhang, Yulin; Hu, Yanning; Shen, Fangfang; Ping-bang, Wang; Yang, Junwen; Liu, Yulei; Lu, Binghuai

doi:10.1128/spectrum.05231-22

Cited by 8 publications

(11 citation statements)

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“…However, the prevalent occurrence of IS Kpn14 is incompatible with the preexisting studies stating that IS5 family elements cause the most frequent inactivation of mgrB [ 9 ]. This might be attributed to the different geographical regions in which the studies were conducted, hence, studies from Saudi Arabia and China were consistent with our findings [ 62 , 63 ]. IS Kpn14 transposed at nucleotide positions − 37, + 35, + 81, + 118, and + 119 with the first transposition being in the promoter region which is presumed to negatively impact the expression of the gene [ 12 ] and the remaining transpositions being within mgrB resulting in gene splitting and generation of malfunctioning MgrB [ 64 ].…”

Section: Discussionsupporting

confidence: 90%

“…Other mutations in PmrC and across arnBCADTEF operon (Fig. 3 ) reflected the divergent mutation profiles displayed by ColRKp isolates as stated by earlier reports [ 63 , 72 ], however, the contribution of these mutations to colistin resistance remains to be unclear and requires further investigation and validation.…”

Section: Discussionsupporting

confidence: 67%

“…CrrAB, an additional 2CS, was completely absent in isolates of ST14 and ST383 lineages. The absence of this system is not reported to be associated with colistin resistance [ 63 ] due to its variable presence in K. pneumoniae strains [ 73 ].…”

Section: Discussionmentioning

confidence: 99%

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Genomic characterization of colistin-resistant Klebsiella pneumoniae isolated from intensive care unit patients in Egypt

Attalla,

Khalil,

Zakaria

et al. 2023

Ann Clin Microbiol Antimicrob

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Background Egypt has witnessed elevated incidence rates of multidrug-resistant Klebsiella pneumoniae infections in intensive care units (ICUs). The treatment of these infections is becoming more challenging whilst colistin-carbapenem-resistant K. pneumoniae is upsurging. Due to the insufficiently available data on the genomic features of colistin-resistant K. pneumoniae in Egypt, it was important to fill in the gap and explore the genomic characteristics, as well as the antimicrobial resistance, the virulence determinants, and the molecular mechanisms of colistin resistance in such a lethal pathogen. Methods Seventeen colistin-resistant clinical K. pneumoniae isolates were collected from ICUs in Alexandria, Egypt in a 6-month period in 2020. Colistin resistance was phenotypically detected by modified rapid polymyxin Nordmann/Poirel and broth microdilution techniques. The isolates susceptibility to 20 antimicrobials was determined using Kirby-Bauer disk diffusion method. Whole genome sequencing and bioinformatic analysis were employed for exploring the virulome, resistome, and the genetic basis of colistin resistance mechanisms. Results Out of the tested K. pneumoniae isolates, 82.35% were extensively drug-resistant and 17.65% were multidrug-resistant. Promising susceptibility levels towards tigecycline (88.24%) and doxycycline (52.94%) were detected. Population structure analysis revealed seven sequence types (ST) and K-types: ST383-K30, ST147-K64, ST17-K25, ST111-K63, ST11-K15, ST14-K2, and ST525-K45. Virulome analysis revealed yersiniabactin, aerobactin, and salmochelin siderophore systems in ˃ 50% of the population. Hypervirulence biomarkers, iucA (52.94%) and rmpA/A2 (5.88%) were detected. Extended-spectrum β-lactamase- and carbapenemase-producers accounted for 94.12% of the population, with blaCTX-M-15, blaNDM-5, and blaOXA-48 reaching 64.71%, 82.35%, and 82.35%, respectively. Chromosomal alterations in mgrB (82.35%) were the most prevailing colistin resistance-associated genetic change followed by deleterious mutations in ArnT (23.53%, L54H and G164S), PmrA (11.76%, G53V and D86E), PmrB (11.76%, T89P and T134P), PmrC (11.76%, S257L), PhoQ (5.88%, L322Q and Q435H), and ArnB (5.88%, G47D) along with the acquisition of mcr-1.1 by a single isolate of ST525. Conclusions In this study, we present the genotypic colistin resistance mechanisms in K. pneumoniae isolated in Egypt. More effective antibiotic stewardship protocols must be implemented by Egyptian health authorities to restrain this hazard and safeguard the future utility of colistin. This is the first characterization of a complete sequence of mcr-1.1-bearing IncHI2/IncHI2A plasmid recovered from K. pneumoniae clinical isolate belonging to the emerging high-risk clone ST525.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 67%

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Genomic characterization of colistin-resistant Klebsiella pneumoniae isolated from intensive care unit patients in Egypt

Attalla,

Khalil,

Zakaria

et al. 2023

Ann Clin Microbiol Antimicrob

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“…Then KQ20605 genome was used as the reference to compare the identity of the above genes among KQ20605, KQ20786, KQ20605-1, KQ20605-2, and KQ20605-5. The PROVEAN platform ( http://provean.jcvi.org/index.php ) was used to predict alterations in the biological functions of the above-described proteins ( Li et al., 2023 ).…”

Section: Methodsmentioning

confidence: 99%

Within-host acquisition of colistin-resistance of an NDM-producing Klebsiella quasipneumoniae subsp. similipneumoniae strain through the insertion sequence-903B-mediated inactivation of mgrB gene in a lung transplant child in China

Wu,

Zhao,

et al. 2023

Front. Cell. Infect. Microbiol.

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BackgroundColistin, as the antibiotic of “last resort” for carbapenem-resistant Klebsiella, develop resistance during administration of this antimicrobial agent. We identified an NDM-1-producing Klebsiella quasipneumonuae subsp. similipneumoniae (KQSS) strain KQ20605 recovered from a child, which developed resistance to colistin (KQ20786) through acquiring an IS903B element between the -27th and -26th bp of mgrB promoter region after 6-day colistin usage.ObjectivesThe aim of this study is to explore the source of IS903B in the disruptive mgrB gene and its underlying mechanisms.Materials and methodsAntibiotics susceptibility testing was conducted via microbroth dilution method. The in vitro colistin-induced experiment of KQ20605 was performed to mimic the in vivo transition from colistin-sensitive to resistant. Whole-genome sequencing was used to molecular identification of colistin resistance mechanism.ResultsThe IS903B element integrated into mgrB gene of KQ20786 had a 100% nucleotide identity and coverage match with one IS903B on plasmid IncR, and only 95.1% (1005/1057) identity to those on chromosome. In vitro, upon the pressure of colistin, KQ20605 could also switch its phenotype from colistin-sensitive to resistant with IS elements (e.g., IS903B and IS26) frequently inserted into mgrB gene at “hotspots”, with the insertion site of IS903B nearly identical to that of KQ20786. Furthermore, IS26 elements in this isolate were only encoded by plasmids, including IncR and conjugative plasmid IncN harboring blaNDM.ConclusionMobilizable IS elements on plasmids tend to be activated and integrated into mgrB gene at “hotspots” in this KQSS, thereby causing the colistin resistance emergence and further dissemination.

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“…Additionally, when maternal sepsis patients arrive at tertiary hospitals, they are given immediately antibiotics such as trimethoprim-sulfamethoxazole, ampicillin, cipro oxacin, cefepime, aztreonam, ceftriaxone, amoxicillin, gentamicin, clindamycin, vancomycin, piperacillintazobactam, and tigecycline. In cases of severe maternal sepsis, physicians often use a combination of two or three cephalosporins, carbapenems, aminoglycosides, and polymyxins [31][32][33]. If these antimicrobial agents fail, the recommended treatment for maternal sepsis is tigecycline combination therapy with avibactam/ceftazidime, or imipenem/meropenem caused by MDR-/XDR-/PDR-K. pneumoniae [34][35][36][37].…”

Section: Introductionmentioning

confidence: 99%

Epidemiology, antimicrobial resistance profile and management of Carbapenem-resistant Klebsiella pneumoniae among mothers with suspected sepsis in Ethiopia

Gadisa

2024

Clinica Chimica Acta

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Genetic Diversity of Polymyxin-Resistance Mechanisms in Clinical Isolates of Carbapenem-Resistant Klebsiella pneumoniae: a Multicenter Study in China

Abstract: Polymyxin-resistant CRKP is a serious public health threat whose resistance mechanisms should be under continuous surveillance. Here, we collected 662 nonduplicate CRKP strains across China to identify the carbapenemase and polymyxin resistance genes and epidemiological features.

Cited by 8 publications

References 50 publications

Genomic characterization of colistin-resistant Klebsiella pneumoniae isolated from intensive care unit patients in Egypt

Genomic characterization of colistin-resistant Klebsiella pneumoniae isolated from intensive care unit patients in Egypt

Within-host acquisition of colistin-resistance of an NDM-producing Klebsiella quasipneumoniae subsp. similipneumoniae strain through the insertion sequence-903B-mediated inactivation of mgrB gene in a lung transplant child in China

Epidemiology, antimicrobial resistance profile and management of Carbapenem-resistant Klebsiella pneumoniae among mothers with suspected sepsis in Ethiopia

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