GM000287 is a conserved determinant of serum resistance and virulence in Klebsiella pneumoniae
7 affiliations
- 1School of Public Health and Emergency Management, School of Medicine, Southern University of Science and Technology, Shenzhen, China
- 2SUSTech Homeostatic Medicine Institute, School of Medicine, Southern University of Science and Technology, Shenzhen, China
- 3School of Medicine, Southern University of Science and Technology, Shenzhen, China
- 4State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- 5School of Physical Science and Technology, Shanghai Tech University, Shanghai, China
- 6Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Department of Pathogen Biology, Shenzhen University Medical School, Shenzhen University, Shenzhen, China
- 7Shenzhen Key Laboratory of Respiratory Diseases, Shenzhen Clinical Research Center for Respiratory Disease, Shenzhen Institute of Respiratory Diseases, Shenzhen People's Hospital (The First Affiliated Hospital, Southern University of Science and Technology, The Second Clinical Medical College, Jinan University), Shenzhen, China
Abstract
Klebsiella pneumoniae (Kp) is an opportunistic Gram-negative pathogen responsible for severe community- and healthcare-associated infections. Resistance to complement-mediated killing is an important determinant of Kp survival in human serum, yet mechanisms beyond capsular polysaccharide-mediated protection remain incompletely understood. Here, using comparative proteomic approaches, we identified a previously uncharacterized protein, GM000287, as a conserved determinant of serum resistance and virulence in Kp. Human serum exposure induced expression of the bacterial type II secretion system (T2SS), and deletion of the essential T2SS components GspD/GspE increased susceptibility to human serum killing. Importantly, disruption of GspD/GspE attenuated virulence in a murine pneumonia model. Comparative secretome analysis identified GM000287 as a T2SS-associated envelope protein that contributes to serum survival. Loss of GM000287 increased C3b production and factor B deposition on the bacterial surface during human serum exposure, consistent with enhanced alternative pathway amplification. In a murine pneumonia model, deletion of GM000287 reduced bacterial persistence and dissemination and attenuated virulence. Given the minimal bactericidal activity of mouse serum against Kp, indicating an additional role for GM000287 during infection. Importantly, GM000287 was highly conserved among Klebsiella species and broadly distributed among members of the Enterobacteriaceae family, and its contribution to serum resistance was validated in genetically diverse Kp clinical isolates. Together, these findings identify GM000287 as a conserved determinant of human serum resistance and in vivo virulence and reveal distinct contributions of GM000287 to K. pneumoniae fitness across different host-associated environments. Author summary: Klebsiella pneumoniae (Kp) is a major human pathogen responsible for severe infections, including pneumonia and bloodstream infections. To establish infection, Kp must withstand multiple host antimicrobial pressures, including complement-mediated killing in human serum; however, mechanisms beyond the well-characterized capsule-mediated resistance remain incompletely understood. Here, we identified GM000287, a previously uncharacterized and highly conserved protein, as an important determinant of human serum resistance and in vivo virulence. Comparative proteomic analysis identified GM000287 as a T2SS-associated envelope protein. Functional studies showed that GM000287 was required for optimal survival in human serum. Loss of GM000287 increased C3b production and factor B deposition on the bacterial surface during human serum exposure, consistent with enhanced alternative pathway amplification. Separately, deletion of GM000287 markedly attenuated Kp in a murine pneumonia model, resulting in reduced bacterial persistence and dissemination. Importantly, GM000287 was broadly conserved among Klebsiella species and related members of the Enterobacteriaceae family, and its contribution to serum resistance is conserved across genetically diverse Kp isolates. Together, these findings reveal a previously unrecognized bacterial factor with distinct contributions to human serum resistance and bacterial fitness during Kp infection.
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BibTeX
@article{lin2026gm000287,
title = {{GM000287 is a conserved determinant of serum resistance and virulence in Klebsiella pneumoniae}},
author = {Xiaomin Lin and Junjun Jia and Zilin Zhuang and Yixin Mo and Xiaoxin Pan and Kaining Zhong and Ping Shen and Quanjiang Ji and Kai Zhou and Liang Yang and Yonghong Xiao and Chunfu Yang},
journal = {PLOS Pathogens},
year = {2026},
month = sep,
doi = {10.1371/journal.ppat.1014619},
url = {https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014619},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - GM000287 is a conserved determinant of serum resistance and virulence in Klebsiella pneumoniae
AU - Xiaomin Lin
AU - Junjun Jia
AU - Zilin Zhuang
AU - Yixin Mo
AU - Xiaoxin Pan
AU - Kaining Zhong
AU - Ping Shen
AU - Quanjiang Ji
AU - Kai Zhou
AU - Liang Yang
AU - Yonghong Xiao
AU - Chunfu Yang
PY - 2026
DA - 2026/09/24
JO - PLOS Pathogens
DO - 10.1371/journal.ppat.1014619
UR - https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014619
AB - Klebsiella pneumoniae (Kp) is an opportunistic Gram-negative pathogen responsible for severe community- and healthcare-associated infections. Resistance to complement-mediated killing is an important determinant of Kp survival in human serum, yet mechanisms beyond capsular polysaccharide-mediated protection remain incompletely understood. Here, using comparative proteomic approaches, we identified a previously uncharacterized protein, GM000287, as a conserved determinant of serum resistance and virulence in Kp. Human serum exposure induced expression of the bacterial type II secretion system (T2SS), and deletion of the essential T2SS components GspD/GspE increased susceptibility to human serum killing. Importantly, disruption of GspD/GspE attenuated virulence in a murine pneumonia model. Comparative secretome analysis identified GM000287 as a T2SS-associated envelope protein that contributes to serum survival. Loss of GM000287 increased C3b production and factor B deposition on the bacterial surface during human serum exposure, consistent with enhanced alternative pathway amplification. In a murine pneumonia model, deletion of GM000287 reduced bacterial persistence and dissemination and attenuated virulence. Given the minimal bactericidal activity of mouse serum against Kp, indicating an additional role for GM000287 during infection. Importantly, GM000287 was highly conserved among Klebsiella species and broadly distributed among members of the Enterobacteriaceae family, and its contribution to serum resistance was validated in genetically diverse Kp clinical isolates. Together, these findings identify GM000287 as a conserved determinant of human serum resistance and in vivo virulence and reveal distinct contributions of GM000287 to K. pneumoniae fitness across different host-associated environments. Author summary: Klebsiella pneumoniae (Kp) is a major human pathogen responsible for severe infections, including pneumonia and bloodstream infections. To establish infection, Kp must withstand multiple host antimicrobial pressures, including complement-mediated killing in human serum; however, mechanisms beyond the well-characterized capsule-mediated resistance remain incompletely understood. Here, we identified GM000287, a previously uncharacterized and highly conserved protein, as an important determinant of human serum resistance and in vivo virulence. Comparative proteomic analysis identified GM000287 as a T2SS-associated envelope protein. Functional studies showed that GM000287 was required for optimal survival in human serum. Loss of GM000287 increased C3b production and factor B deposition on the bacterial surface during human serum exposure, consistent with enhanced alternative pathway amplification. Separately, deletion of GM000287 markedly attenuated Kp in a murine pneumonia model, resulting in reduced bacterial persistence and dissemination. Importantly, GM000287 was broadly conserved among Klebsiella species and related members of the Enterobacteriaceae family, and its contribution to serum resistance is conserved across genetically diverse Kp isolates. Together, these findings reveal a previously unrecognized bacterial factor with distinct contributions to human serum resistance and bacterial fitness during Kp infection.
SN - 1553-7374
ER -