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Potential therapeutic targets of Klebsiella pneumoniae: a multi-omics review perspective

BRIEFINGS IN FUNCTIONAL GENOMICS (2022)

Journal

BRIEFINGS IN FUNCTIONAL GENOMICS

Volume 21, Issue 2, Pages 63-77

Publisher

OXFORD UNIV PRESS

DOI: 10.1093/bfgp/elab038

Keywords

Gram-negative bacteria; Klebsiella pneumoniae; drug targets; drug resistance; structural genomics; virulence factors

Funding

Indian Council of Medical Research [ECD/Adhoc/2/2021-22]

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Abstract

The prolonged use of antibiotics has led to the development of multidrug resistance in many organisms, causing a global health crisis. Klebsiella pneumoniae is a causative organism for various infections and recently, both immunocompromised and healthy individuals are equally susceptible to K. pneumoniae infections due to the emergence of hypervirulent strains. This review discusses the pathophysiology of K. pneumoniae, including its virulence determinants, and explores potential drug targets for the discovery of novel drugs and effective treatment regimens.

The multidrug resistance developed in many organisms due to the prolonged use of antibiotics has been an increasing global health crisis. Klebsiella pneumoniae is a causal organism for various infections, including respiratory, urinary tract and biliary diseases. Initially, immunocompromised individuals are primarily affected by K. pneumoniae. Due to the emergence of hypervirulent strains recently, both healthy and immunocompetent individuals are equally susceptible to K. pneumoniae infections. The infections caused by multidrug-resistant and hypervirulent K. pneumoniae strains are complicated to treat, illustrating an urgent need to develop novel and more practical approaches to combat the pathogen. We focused on the previously performed high-throughput analyses by other groups to discover several novel enzymes that may be considered attractive drug targets of K. pneumoniae. These targets qualify most of the selection criteria for drug targeting, including an absence of its homolog's gene in the host. The capsule, lipopolysaccharide, fimbriae, siderophores and essential virulence factors facilitate the pathogen entry, infection and survival inside the host. This review discusses K. pneumoniae pathophysiology, including its virulence determinants and further the potential drug targets that might facilitate the discovery of novel drugs and effective treatment regimens shortly.

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Impact of Polymyxin Resistance on Virulence and Fitness among Clinically Important Gram-Negative Bacteria

Yuan Wang, Qixia Luo, Tingting Xiao, Yunying Zhu, Yonghong Xiao

Summary: Humanity is facing a growing threat from multi-drug resistant Gram-negative bacteria, particularly Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii. The last-line treatment, polymyxin, is facing challenges due to the occurrence of polymyxin-resistant bacteria. Understanding the impact of polymyxin resistance on the virulence and fitness of these bacteria is crucial for prevention and intervention.

ENGINEERING (2022)