AUTHOR=Li Pu , Zhang Sirui , Wang Jingdan , Al-Shamiri Mona Mohamed , Luo Kai , Liu Shuyan , Mi Peng , Wu Xiaokang , Liu Haiping , Tian Huohuan , Han Bei , Lei Jin’e , Han Shaoshan , Han Lei 

TITLE=The role of type VI secretion system genes in antibiotic resistance and virulence in Acinetobacter baumannii clinical isolates

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=14

YEAR=2024

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2024.1297818

DOI=10.3389/fcimb.2024.1297818

ISSN=2235-2988

ABSTRACT=<sec><title>Introduction</title><p>The type VI secretion system (T6SS) is a crucial virulence factor in the nosocomial pathogen <italic>Acinetobacter baumannii</italic>. However, its association with drug resistance is less well known. Notably, the roles that different T6SS components play in the process of antimicrobial resistance, as well as in virulence, have not been systematically revealed.</p></sec><sec><title>Methods</title><p>The importance of three representative T6SS core genes involved in the drug resistance and virulence of <italic>A. baumannii</italic>, namely, <italic>tssB</italic>, <italic>tssD</italic> (<italic>hcp</italic>), and <italic>tssM</italic> was elucidated.</p></sec><sec><title>Results</title><p>A higher ratio of the three core genes was detected in drug-resistant strains than in susceptible strains among our 114 <italic>A. baumannii</italic> clinical isolates. Upon deletion of <italic>tssB</italic> in AB795639, increased antimicrobial resistance to cefuroxime and ceftriaxone was observed, alongside reduced resistance to gentamicin. The Δ<italic>tssD</italic> mutant showed decreased resistance to ciprofloxacin, norfloxacin, ofloxacin, tetracycline, and doxycycline, but increased resistance to tobramycin and streptomycin. The <italic>tssM</italic>-lacking mutant showed an increased sensitivity to ofloxacin, polymyxin B, and furazolidone. In addition, a significant reduction in biofilm formation was observed only with the Δ<italic>tssM</italic> mutant. Moreover, the Δ<italic>tssM</italic> strain, followed by the Δ<italic>tssD</italic> mutant, showed decreased survival in human serum, with attenuated competition with <italic>Escherichia coli</italic> and impaired lethality in <italic>Galleria mellonella</italic>.</p></sec><sec><title>Discussion</title><p>The above results suggest that T6SS plays an important role, participating in the antibiotic resistance of <italic>A. baumannii</italic>, especially in terms of intrinsic resistance. Meanwhile, <italic>tssM</italic> and <italic>tssD</italic> contribute to bacterial virulence to a greater degree, with tssM being associated with greater importance.</p></sec>