Study on the characteristics and pathogenic mechanism of carbapenem-resistant Klebsiella pneumoniae

doi:10.3877/cma.j.issn.1674-6902.2025.03.015

Abstract

Abstract:

Objective

To analyze the molecular characteristics，resistance patterns，virulence factors，and pathogenic mechanisms of carbapenem-resistant Klebsiella pneumoniae（CRKP）.

Methods

Eighty CRKP strains isolated from our hospital between January 2018 and December 2023 were selected，and clinical data were collected. Thirty-five strains were randomly chosen for antimicrobial susceptibility testing using the disk diffusion method. Metagenomic next-generation sequencing （mNGS） was performed for sequencing CRKP isolates，and capsular serotyping was conducted for strain classification.

Results

Among the 80 CRKP strains，capsular serotypes included K1 12 strains（ 15.00%），K2 3 strains（ 3.75%），K35 1 strain（1.25%），K57 1 strain（1.25%），and 63 strains （78.75%） were untypeable. Resistance rates to ciprofloxacin and tetracycline were 77.50% and 61.25%，respectively，while resistance to common antimicrobial agents exceeded 90%.Carbapenemase genes identified were KPC-2（60.00%），NDM（20.00%），and OXA-48（8.57%）； one strain co-produced OXA-48 and NDM. Aminoglycoside-modifying enzyme genes included aac（6'）-Ⅰb（28.57%）；one strain carried aac（6'）-Ⅰb and aac（3）-Ⅰa，and two strains carried aac（6'）-Ⅰb and aac（3）-Ⅳa. No methyltransferase genes were detected. Capsular antigen molecular typing predominantly identified KL1 and KL2. O-antigen types included O1/O2v1 16 strains （45.71%），O1/O2v2 12 strains（34.28%），O3b 2 strains（ 5.71%），and O4 1 strain（2.85%）. Virulence genes with high detection rates were entB（100.00%），mrkD（97.14%），ybtS（94.28%），and rmpA（11.43%）. GO gene functions were related to metabolic processes （P＜0.001）. CRKP primarily carried ColRNAI and IncFIB（K） plasmids，with sdiA present in most conjugative plasmids.

Conclusion

CRKP exhibits high resistance to common antimicrobials，predominantly mediated by carbapenemase genes and aminoglycoside-modifying genes. High positivity rates were observed for virulence genes entB，mrkD，and ybtS. An OXA-48-producing K1 capsular hypervirulent strain was identified.

Key words: Carbapenem-resistant Klebsiella pneumoniae, Molecular typing, Drug resistance gene, Virulence gene, Carbapenemase gene

Yingyi Cao, Liting Dai, Yanrong Lai, Wenqiang Feng, Peibo Yuan, Dingqiang Chen. Study on the characteristics and pathogenic mechanism of carbapenem-resistant Klebsiella pneumoniae[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2025, 18(03): 423-428.

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Figures/Tables 6

References 30

1	Stojowska-Swᶒdrzyńska K，Łupkowska A，Kuczyńska-Wisnik D，et al. Antibiotic heteroresistance in Klebsiella pneumoniae［J］. Int J Molecul Sci，2021，23（1）：449.
2	Gonzalez-Ferrer S，Peñaloza HF，Budnick JA，et al. Finding order in the chaos：outstanding questions in Klebsiella pneumoniae pathogenesis［J］. Infect Immun，2021，89（4）：e00693-20.
3	Hu Y，Anes J，Devineau S，et al. Klebsiella pneumoniae：Prevalence，reservoirs，antimicrobial resistance，pathogenicity，and infection：A Hitherto Unrecognized Zoonotic Bacterium［J］. Foodborne Pathog Dis，2021，18（2）：63-84.
4	Yang X，Dong N，Chan EWC，et al. Carbapenem resistance-encoding and virulence-encoding conjugative plasmids in Klebsiella pneumoniae［J］. Trends Microbiol，2021，29（1）：65-83.
5	Lai CC，Yu WL. Klebsiella pneumoniae Harboring Carbapenemase Genes in Taiwan：Its evolution over 20 years，1998-2019［J］. Int J Antimicrob Agents，2021，58（1）：106354.
6	段炜，范沁林，刘勇. 替加环素对NICU 碳青霉烯耐药菌致院内获得性肺炎抗感染疗效的回顾性分析［J/CD］. 中华肺部疾病杂志（电子版），2019，12（3）：315-320.
7	Gardos G，Cole JO. Maintenance antipsychotic therapy：is the cure worse than the disease？［J］. Am J Psych，1976，133（1）：32-36.
8	Xu L，Li J，Wu W，et al.Klebsiella pneumoniae capsular polysaccharide：Mechanism in regulation of synthesis，virulence，and pathogenicity［J］. Virulence，2024，15（1）：2439509.
9	全国细菌耐药监测网. 全国碳青霉烯类耐药肺炎克雷伯菌对抗菌药物的敏感性、耐药机制和分子特征研究［J］. 中华检验医学杂志，2024，47（6）：629-638.
10	Yang Y，Yang Y，Chen G，et al. Molecular characterization of carbapenem-resistant and virulent plasmids in Klebsiella pneumoniae from patients with bloodstream infections in China［J］. Emerg Micr Infect，2021，10（1）：700-709.
11	Ljungquist O，Magda M，Giske CG，et al. Pandrug-resistant Klebsiella pneumoniae isolated from Ukrainian war victims are hypervirulent［J］. J Infect，2024，89（6）：106312.
12	张丽，朱元祺，张小兵，等. 耐碳青霉烯类肺炎克雷伯菌的耐药基因检测［J］. 中华医院感染学杂志，2014（23）：5734-5736，5745.
13	Humphries R，Bobenchik AM，Hindler JA，et al. Overview of changes to the clinical and laboratory standards institute performance standards for antimicrobial susceptibility testing，M100，31st Edition［J］. J Clin Microbiol，2021，59（12）：e00213-21.
14	Huang DW，Sherman BT，Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources［J］. Nat Protoc，2009，4（1）：44-57.
15	Sherman BT，Hao M，Qiu J，et al. DAVID：a web server for functional enrichment analysis and functional annotation of gene lists（2021 update）［J］. Nucleic Acids Res，2022，50（W1）：W216-W221.
16	Lee AJ，Suh H. Klebsiella pneumoniae ST11 producing GES-5 carbapenemase isolated from tertiary-care hospital［J］. Clin Lab，2021，67（10/2021）：doi：10.7754/Clin.Lab.2021.201120.
17	Han YL，Wen XH，Zhao W，et al. Epidemiological characteristics and molecular evolution mechanisms of carbapenem-resistant hypervirulent Klebsiella pneumoniae［J］. Front Microbiol，2022，13：1003783.
18	李冉，梁玉宜，苏歆，等. 广州某三甲医院耐碳青霉烯类肺炎克雷伯菌耐药及毒力基因分析［J］. 国际检验医学杂志，2024，45（22）：2773-2778.
19	Wang M，Earley M，Chen L，et al. Clinical outcomes and bacterial characteristics of carbapenem-resistant Klebsiella pneumoniae complex among patients from different global regions （CRACKLE-2）：a prospective，multicentre，cohort study［J］. Lancet Infect Dis，2022，22（3）：401-412.
20	Cui Z，Wang L，Feng M. Clinical and epidemiological characteristics of carbapenem-resistant Klebsiella pneumoniae infections in a tertiary hospital in China［J］. Microb Drug Res，2023，29（9）：401-406.
21	Shi Q，Shen S，Tang C，et al. Molecular mechanisms responsible KPC-135-mediated resistance to ceftazidime-avibactam in ST11-K47 hypervirulent Klebsiella pneumoniae ［J］. Emerg Microb Infect，2024，13（1）：2361007.
22	Li L，Li S，Wei X，et al. Infection with carbapenem-resistant hypervirulent Klebsiella pneumoniae：clinical，virulence and molecular epidemiological characteristics［J］. Antimicrob Resist Infect Control，2023，12（1）：124.
23	Dangor Z，Benson N，Berkley JA，et al. Vaccine value profile for Klebsiella pneumoniae［J］. Vaccine，2024，42（19）：S125-S141.
24	Beig M，Aghamohammad S，Majidzadeh N，et al. Antibiotic resistance rates in hypervirulent Klebsiella pneumoniae strains：A systematic review and meta-analysis［J］. J Glob Antimicrob Resist，2024，38：376-388.
25	Tayek JA，Bistrian BR，Blackburn GL. The effects of acute clostridium difficile diarrhea on fecal nitrogen content in adult hospitalized patients［J］. J Am Coll Nutrit，1987，6（3）：255-259.
26	Aslan AT，Kirbaş E，Sancak B，et al. A retrospective observational cohort study of the clinical epidemiology of bloodstream infections due to carbapenem-resistant Klebsiella pneumoniae in an OXA-48 endemic setting［J］. Int J Antimicrob Agents，2022，59（4）：106554.
27	Huang Y，Rana AP，Wenzler E，et al. Aminoglycoside-resistance gene signatures are predictive of aminoglycoside MICs for carbapenem-resistant Klebsiella pneumoniae ［J］. J Antimicrob Chemoth，2022，77（2）：356-363.
28	Han R，Niu M，Liu S，et al. The effect of siderophore virulence genes entB and ybtS on the virulence of Carbapenem-resistant Klebsiella pneumoniae［J］. Microb Pathogen，2022，171：105746.
29	Fang R，Liu H，Zhang X，et al. Difference in biofilm formation between carbapenem-resistant and carbapenem-sensitive Klebsiella pneumoniae based on analysis of mrkH distribution［J］. Microbial Pathogenesis，2021，152：104743.
30	卞天丹，宋爽，陶臻. 高毒力肺炎克雷伯菌分子学机制研究进展［J/CD］. 中华肺部疾病杂志（电子版），2023，16（3）：438-441.

抗菌药物	CRKP 菌株（n = 80）	K1（n = 12）	其他 K 型（n = 68）
亚胺培南	80(100.00)	12(100.00)	68(100.00)
美罗培南	80(100.00)	12(100.00)	68(100.00)
厄他培南	78(97.50)	12(100.00)	66(97.06)
头孢西丁	80(100.00)	12(100.00)	68(100.00)
头孢噻肟	79(98.75)	12(100.00)	67(98.53)
头孢他啶	73(91.25)	11(91.67)	62(91.18)
环丙沙星	62(77.50)	9(75.00)	53(77.94)
左氧氟沙星	74(92.50)	11(91.67)	63(92.65)
四环素	49(61.25)	8(66.67)	41(60.29)
庆大霉素	76(95.00)	12(100.00)	64(91.42)
阿米卡星	77(96.25)	12(100.00)	65(95.59)

抗菌药物	CRKP 菌株（n = 80）	K1（n = 12）	其他 K 型（n = 68）
亚胺培南	80(100.00)	12(100.00)	68(100.00)
美罗培南	80(100.00)	12(100.00)	68(100.00)
厄他培南	78(97.50)	12(100.00)	66(97.06)
头孢西丁	80(100.00)	12(100.00)	68(100.00)
头孢噻肟	79(98.75)	12(100.00)	67(98.53)
头孢他啶	73(91.25)	11(91.67)	62(91.18)
环丙沙星	62(77.50)	9(75.00)	53(77.94)
左氧氟沙星	74(92.50)	11(91.67)	63(92.65)
四环素	49(61.25)	8(66.67)	41(60.29)
庆大霉素	76(95.00)	12(100.00)	64(91.42)
阿米卡星	77(96.25)	12(100.00)	65(95.59)

耐药基因	CRKP 菌株（n=35）	KL1（n=7）	其他 K 型（n=28）
KPC-2	21(60.00)	3(42.86)	18(64.28)
NDM	7(20.00)	2(28.57)	5(17.85)
OXA-48	3(8.57)	1(14.29)	2(7.14)
IMP	0(0.00)	0(0.00)	0(0.00)
VIM	2(5.71)	0(0.00)	2(7.14)
GES	0(0.00)	0(0.00)	0(0.00)
aac (6’)-Ⅰb	10(28.57)	2(28.57)	8(28.57)
aac (3)-Ⅱa	3(8.57)	0(0.00)	3(10.71)
aac (3)-Ⅰa	3(8.57)	0(0.00)	3(10.71)
aac (3)-Ⅳa	4(11.43)	1(14.29)	3(10.71)
ant (2″)-Ⅰa	1(2.86)	0(0.00)	1(3.57)
armA	0(0.00)	0(0.00)	0(0.00)
rmtB	0(0.00)	0(0.00)	0(0.00)
rmtC	0(0.00)	0(0.00)	0(0.00)

耐药基因	CRKP 菌株（n=35）	KL1（n=7）	其他 K 型（n=28）
KPC-2	21(60.00)	3(42.86)	18(64.28)
NDM	7(20.00)	2(28.57)	5(17.85)
OXA-48	3(8.57)	1(14.29)	2(7.14)
IMP	0(0.00)	0(0.00)	0(0.00)
VIM	2(5.71)	0(0.00)	2(7.14)
GES	0(0.00)	0(0.00)	0(0.00)
aac (6’)-Ⅰb	10(28.57)	2(28.57)	8(28.57)
aac (3)-Ⅱa	3(8.57)	0(0.00)	3(10.71)
aac (3)-Ⅰa	3(8.57)	0(0.00)	3(10.71)
aac (3)-Ⅳa	4(11.43)	1(14.29)	3(10.71)
ant (2″)-Ⅰa	1(2.86)	0(0.00)	1(3.57)
armA	0(0.00)	0(0.00)	0(0.00)
rmtB	0(0.00)	0(0.00)	0(0.00)
rmtC	0(0.00)	0(0.00)	0(0.00)

耐药基因	CRKP 菌株（n=35）	K1（n=7）	其他 K 型（n=28）
magA	0(0.00)	0(0.00)	0(0.00)
mrkD	34(97.14)	7(100.00)	27(96.43)
entB	35(100.00)	7(100.00)	28(100.00)
ybtS	33(94.29)	7(100.00)	26(92.86)
kfu	1(2.86)	0(0.00)	1(3.57)
iutA	2(5.71)	1(14.29)	1(3.57)
allS	1(2.86)	0(0.00)	1(3.57)
rmpA	4(11.43)	2(28.57)	2(7.14)

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