OmpK35 and OmpK36 Deficiencies Driving High-level Carbapenem Resistance in ST11 Klebsiella Pneumoniae

Jiayuan Qin; Yu Feng; Yongqiang Yang; Alan McNally; Zhiyong Zong

doi:10.1093/infdis/jiaf621

OmpK35 and OmpK36 Deficiencies Driving High-level Carbapenem Resistance in ST11 Klebsiella Pneumoniae

Jiayuan Qin
, Yu Feng
, Yongqiang Yang
, Alan McNally
, Zhiyong Zong

Microbes, Infection and Microbiomes

Research output: Contribution to journal › Article › peer-review

Abstract

Background: Factors contributing to the success of carbapenem-resistant Klebsiella pneumoniae (CRKP) of sequence type 11 (ST11) remain poorly understood.

Methods: All GenBank-available K. pneumoniae genome sequences were retrieved. Isolates from mainland China carrying bla_KPC and exhibiting high-quality assembly were selected for determining ST, virulence factors, antimicrobial resistance genes, plasmid types, and outer membrane porins (OmpK35 and OmpK36). Cloning experiments were performed for complementing porin deficiencies. In vitro growth assays under carbapenem selection pressure and carbon utilization assays were conducted. The structure alteration of OmpK36 with a two-amino-acid Gly-Asp insertion (OmpK36GD) was modeled.

Results: ST11 accounted for 87.22% (8930/10 238) of all bla_KPC-carrying CRKP Chinese strains. The majority (96.13%, 8584/8930) of ST11 CRKP strains had a truncated OmpK35 (OmpK35-del), with a 17%-amino-acid remnant, and OmpK36GD. Only 6.42% (84/1308) of non-ST11 CRKP possessed such alterations. The GD insertion obstructs the outermost channel and compromises OmpK36 function. ST11 CRKP with OmpK35-del and OmpK36GD exhibited higher minimum inhibitory concentrations to carbapenems, which was reduced by complementing wild-type of OmpK35 and/or OmpK36. Strains possessing OmpK35-del and OmpK36GD had better growth under low concentration (2 or 4 mg/L) meropenem. Unlike truncations of OmpK36, OmpK36GD does not interfere with utilizing carbon sources.

Conclusions: OmpK35 deficiency and OmpK36 structure alteration, combined with KPC-2 carbapenemase production, contribute to the high-level carbapenem resistance observed in ST11 CRKP strains. OmpK36GD represents an optimal model for OmpK36 deficiencies due to its minimal fitness cost. With the porin deficiencies, ST11 CRKP strains demonstrate enhanced growth and proliferation under carbapenem selection pressure, likely promoting their prevalence.

Original language	English
Pages (from-to)	S64-S71
Number of pages	8
Journal	The Journal of Infectious Diseases
Volume	233
Issue number	Supplement_1
Early online date	10 Mar 2026
DOIs	https://doi.org/10.1093/infdis/jiaf621
Publication status	Published - 15 Mar 2026

Bibliographical note

© The Author(s) 2026. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact [email protected].

Keywords

Klebsiella pneumoniae/genetics
Porins/genetics
Bacterial Proteins/genetics
Carbapenems/pharmacology
Anti-Bacterial Agents/pharmacology
Klebsiella Infections/microbiology
Humans
Microbial Sensitivity Tests
China
Plasmids/genetics
Virulence Factors/genetics
Carbapenem-Resistant Enterobacteriaceae/genetics
beta-Lactam Resistance/genetics

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10.1093/infdis/jiaf621Licence: None: All rights reserved

QinJ2026OmpK35_AAMAccepted author manuscript, 407 KBLicence: Creative Commons: Attribution (CC BY)

Cite this

@article{e09d12f7bdbd4cb79894f9c516877679,

title = "OmpK35 and OmpK36 Deficiencies Driving High-level Carbapenem Resistance in ST11 Klebsiella Pneumoniae",

abstract = "Background: Factors contributing to the success of carbapenem-resistant Klebsiella pneumoniae (CRKP) of sequence type 11 (ST11) remain poorly understood.Methods: All GenBank-available K. pneumoniae genome sequences were retrieved. Isolates from mainland China carrying blaKPC and exhibiting high-quality assembly were selected for determining ST, virulence factors, antimicrobial resistance genes, plasmid types, and outer membrane porins (OmpK35 and OmpK36). Cloning experiments were performed for complementing porin deficiencies. In vitro growth assays under carbapenem selection pressure and carbon utilization assays were conducted. The structure alteration of OmpK36 with a two-amino-acid Gly-Asp insertion (OmpK36GD) was modeled.Results: ST11 accounted for 87.22\% (8930/10 238) of all blaKPC-carrying CRKP Chinese strains. The majority (96.13\%, 8584/8930) of ST11 CRKP strains had a truncated OmpK35 (OmpK35-del), with a 17\%-amino-acid remnant, and OmpK36GD. Only 6.42\% (84/1308) of non-ST11 CRKP possessed such alterations. The GD insertion obstructs the outermost channel and compromises OmpK36 function. ST11 CRKP with OmpK35-del and OmpK36GD exhibited higher minimum inhibitory concentrations to carbapenems, which was reduced by complementing wild-type of OmpK35 and/or OmpK36. Strains possessing OmpK35-del and OmpK36GD had better growth under low concentration (2 or 4 mg/L) meropenem. Unlike truncations of OmpK36, OmpK36GD does not interfere with utilizing carbon sources.Conclusions: OmpK35 deficiency and OmpK36 structure alteration, combined with KPC-2 carbapenemase production, contribute to the high-level carbapenem resistance observed in ST11 CRKP strains. OmpK36GD represents an optimal model for OmpK36 deficiencies due to its minimal fitness cost. With the porin deficiencies, ST11 CRKP strains demonstrate enhanced growth and proliferation under carbapenem selection pressure, likely promoting their prevalence.",

keywords = "Klebsiella pneumoniae/genetics, Porins/genetics, Bacterial Proteins/genetics, Carbapenems/pharmacology, Anti-Bacterial Agents/pharmacology, Klebsiella Infections/microbiology, Humans, Microbial Sensitivity Tests, China, Plasmids/genetics, Virulence Factors/genetics, Carbapenem-Resistant Enterobacteriaceae/genetics, beta-Lactam Resistance/genetics",

author = "Jiayuan Qin and Yu Feng and Yongqiang Yang and Alan McNally and Zhiyong Zong",

note = "{\textcopyright} The Author(s) 2026. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact [email protected].",

year = "2026",

month = mar,

day = "15",

doi = "10.1093/infdis/jiaf621",

language = "English",

volume = "233",

pages = "S64--S71",

journal = "The Journal of Infectious Diseases",

issn = "0022-1899",

publisher = "Oxford University Press",

number = "Supplement\_1",

}

TY - JOUR

T1 - OmpK35 and OmpK36 Deficiencies Driving High-level Carbapenem Resistance in ST11 Klebsiella Pneumoniae

AU - Qin, Jiayuan

AU - Feng, Yu

AU - Yang, Yongqiang

AU - McNally, Alan

AU - Zong, Zhiyong

N1 - © The Author(s) 2026. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact [email protected].

PY - 2026/3/15

Y1 - 2026/3/15

N2 - Background: Factors contributing to the success of carbapenem-resistant Klebsiella pneumoniae (CRKP) of sequence type 11 (ST11) remain poorly understood.Methods: All GenBank-available K. pneumoniae genome sequences were retrieved. Isolates from mainland China carrying blaKPC and exhibiting high-quality assembly were selected for determining ST, virulence factors, antimicrobial resistance genes, plasmid types, and outer membrane porins (OmpK35 and OmpK36). Cloning experiments were performed for complementing porin deficiencies. In vitro growth assays under carbapenem selection pressure and carbon utilization assays were conducted. The structure alteration of OmpK36 with a two-amino-acid Gly-Asp insertion (OmpK36GD) was modeled.Results: ST11 accounted for 87.22% (8930/10 238) of all blaKPC-carrying CRKP Chinese strains. The majority (96.13%, 8584/8930) of ST11 CRKP strains had a truncated OmpK35 (OmpK35-del), with a 17%-amino-acid remnant, and OmpK36GD. Only 6.42% (84/1308) of non-ST11 CRKP possessed such alterations. The GD insertion obstructs the outermost channel and compromises OmpK36 function. ST11 CRKP with OmpK35-del and OmpK36GD exhibited higher minimum inhibitory concentrations to carbapenems, which was reduced by complementing wild-type of OmpK35 and/or OmpK36. Strains possessing OmpK35-del and OmpK36GD had better growth under low concentration (2 or 4 mg/L) meropenem. Unlike truncations of OmpK36, OmpK36GD does not interfere with utilizing carbon sources.Conclusions: OmpK35 deficiency and OmpK36 structure alteration, combined with KPC-2 carbapenemase production, contribute to the high-level carbapenem resistance observed in ST11 CRKP strains. OmpK36GD represents an optimal model for OmpK36 deficiencies due to its minimal fitness cost. With the porin deficiencies, ST11 CRKP strains demonstrate enhanced growth and proliferation under carbapenem selection pressure, likely promoting their prevalence.

AB - Background: Factors contributing to the success of carbapenem-resistant Klebsiella pneumoniae (CRKP) of sequence type 11 (ST11) remain poorly understood.Methods: All GenBank-available K. pneumoniae genome sequences were retrieved. Isolates from mainland China carrying blaKPC and exhibiting high-quality assembly were selected for determining ST, virulence factors, antimicrobial resistance genes, plasmid types, and outer membrane porins (OmpK35 and OmpK36). Cloning experiments were performed for complementing porin deficiencies. In vitro growth assays under carbapenem selection pressure and carbon utilization assays were conducted. The structure alteration of OmpK36 with a two-amino-acid Gly-Asp insertion (OmpK36GD) was modeled.Results: ST11 accounted for 87.22% (8930/10 238) of all blaKPC-carrying CRKP Chinese strains. The majority (96.13%, 8584/8930) of ST11 CRKP strains had a truncated OmpK35 (OmpK35-del), with a 17%-amino-acid remnant, and OmpK36GD. Only 6.42% (84/1308) of non-ST11 CRKP possessed such alterations. The GD insertion obstructs the outermost channel and compromises OmpK36 function. ST11 CRKP with OmpK35-del and OmpK36GD exhibited higher minimum inhibitory concentrations to carbapenems, which was reduced by complementing wild-type of OmpK35 and/or OmpK36. Strains possessing OmpK35-del and OmpK36GD had better growth under low concentration (2 or 4 mg/L) meropenem. Unlike truncations of OmpK36, OmpK36GD does not interfere with utilizing carbon sources.Conclusions: OmpK35 deficiency and OmpK36 structure alteration, combined with KPC-2 carbapenemase production, contribute to the high-level carbapenem resistance observed in ST11 CRKP strains. OmpK36GD represents an optimal model for OmpK36 deficiencies due to its minimal fitness cost. With the porin deficiencies, ST11 CRKP strains demonstrate enhanced growth and proliferation under carbapenem selection pressure, likely promoting their prevalence.

KW - Klebsiella pneumoniae/genetics

KW - Porins/genetics

KW - Bacterial Proteins/genetics

KW - Carbapenems/pharmacology

KW - Anti-Bacterial Agents/pharmacology

KW - Klebsiella Infections/microbiology

KW - Humans

KW - Microbial Sensitivity Tests

KW - China

KW - Plasmids/genetics

KW - Virulence Factors/genetics

KW - Carbapenem-Resistant Enterobacteriaceae/genetics

KW - beta-Lactam Resistance/genetics

U2 - 10.1093/infdis/jiaf621

DO - 10.1093/infdis/jiaf621

M3 - Article

C2 - 41824647

SN - 0022-1899

VL - 233

SP - S64-S71

JO - The Journal of Infectious Diseases

JF - The Journal of Infectious Diseases

IS - Supplement_1

ER -

OmpK35 and OmpK36 Deficiencies Driving High-level Carbapenem Resistance in ST11 Klebsiella Pneumoniae

Abstract

Bibliographical note

Keywords

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