Acquisition of T6SS Effector TseL Contributes to the Emerging of Novel Epidemic Strains of Pseudomonas aeruginosa

Ren, Anmin1; Jia, Minlu1; Liu, Jihong3; Zhou, Tian1; Wu, Liwen2; Dong, Tao2; Cai, Zhao1; Qu, Jiuxin6; Liu, Yang3; Yang, Liang1,4,5; Zhang, Yingdan1

2022-12-01

10.1128/spectrum.03308-22

Microbiology Spectrum   影响因子和分区

2165-0497

["Pseudomonas aeruginosa is one predominant pathogen that causes hospital-acquired infections and is one of the commonest coinfecting bacteria in immunocompromised patients and chronic wounds. This bacterium harbors a diverse accessory genome with a high frequency of gene recombination, rendering its population highly heterogeneous.","Pseudomonas aeruginosa is an opportunistic pathogen with multiple strategies to interact with other microbes and host cells, gaining fitness in complicated infection sites. The contact-dependent type VI secretion system (T6SS) is one critical secretion apparatus involved in both interbacterial competition and pathogenesis. To date, only limited numbers of T6SS-effectors have been clearly characterized in P. aeruginosa laboratory strains, and the importance of T6SS diversity in the evolution of clinical P. aeruginosa remains unclear. Recently, we characterized a P. aeruginosa clinical strain LYSZa7 from a COVID-19 patient, which adopted complex genetic adaptations toward chronic infections. Bioinformatic analysis has revealed a putative type VI secretion system (T6SS) dependent lipase effector in LYSZa7, which is a homologue of TseL in Vibrio cholerae and is widely distributed in pathogens. We experimentally validated that this TseL homologue belongs to the Tle2, a subfamily of T6SS-lipase effectors; thereby, we name this effector TseL (TseL(PA) in this work). Further, we showed the lipase-dependent bacterial toxicity of TseL(PA), which primarily targets bacterial periplasm. The toxicity of TseL(PA) can be neutralized by two immunity proteins, TsiP1 and TsiP2, which are encoded upstream of tseL. In addition, we proved this TseL(PA) contributes to bacterial pathogenesis by promoting bacterial internalization into host cells. Our study suggests that clinical bacterial strains employ a diversified group of T6SS effectors for interbacterial competition and might contribute to emerging of new epidemic clonal lineages.IMPORTANCE Pseudomonas aeruginosa is one predominant pathogen that causes hospital-acquired infections and is one of the commonest coinfecting bacteria in immunocompromised patients and chronic wounds. This bacterium harbors a diverse accessory genome with a high frequency of gene recombination, rendering its population highly heterogeneous. Numerous Pa lineages coexist in the biofilm, where successful epidemic clonal lineage or strain-specific type commonly acquires genes to increase its fitness over the other organisms. Current studies of Pa genomic diversity commonly focused on antibiotic resistant genes and novel phages, overlooking the contribution of type VI secretion system (T6SS). We characterized a Pa clinical strain LYSZa7 from a COVID-19 patient, which adopted complex genetic adaptations toward chronic infections. We report, in this study, a novel T6SS-lipase effector that is broadly distributed in Pa clinical isolates and other predominant pathogens. The study suggests that hospital transmission may raise the emergence of new epidemic clonal lineages with specified T6SS effectors."]

Pseudomonas aeruginosa T6SS effector TseL pathogenesis

SCI

英语

第一 ; 通讯

Guangdong Natural Science Foundation for Distinguished Young Scholar[2020B1515020003] ; Guangdong Basic and Applied Basic Research Foundation["2019A1515110640","2020A1515010316"] ; Shenzhen Key Laboratory of Gene Regulation and Systems Biology, Southern University of Science and Technology[ZDSYS20200811144002008] ; Shenzhen Science and Technology Program[KQTD20200909113758004]

Microbiology

Microbiology

WOS:000902369300001

AMER SOC MICROBIOLOGY

Web of Science

1.Southern Univ Sci & Technol, Sch Med, Shenzhen, Guangdong, Peoples R China
2.Southern Univ Sci & Technol, Sch Life Sci, Shenzhen, Guangdong, Peoples R China
3.Southern Univ Sci, Technol Hosp, Med Res Ctr, Shenzhen, Guangdong, Peoples R China
4.Southern Univ Sci & Technol, Shenzhen Peoples Hosp 3, Natl Clin Res Ctr Infect Dis, Affiliated Hosp 2, Shenzhen, Guangdong, Peoples R China
5.Southern Univ Sci & Technol, Key Univ Lab Metab & Hlth Guangdong, Shenzhen, Guangdong, Peoples R China
6.Southern Univ Sci & Technol, Shenzhen Peoples Hosp 3, Affiliated Hosp 2, Shenzhen, Guangdong, Peoples R China

Ren, Anmin,Jia, Minlu,Liu, Jihong,et al. Acquisition of T6SS Effector TseL Contributes to the Emerging of Novel Epidemic Strains of Pseudomonas aeruginosa[J]. Microbiology Spectrum,2022,11(1).

Ren, Anmin.,Jia, Minlu.,Liu, Jihong.,Zhou, Tian.,Wu, Liwen.,...&Zhang, Yingdan.(2022).Acquisition of T6SS Effector TseL Contributes to the Emerging of Novel Epidemic Strains of Pseudomonas aeruginosa.Microbiology Spectrum,11(1).

Ren, Anmin,et al."Acquisition of T6SS Effector TseL Contributes to the Emerging of Novel Epidemic Strains of Pseudomonas aeruginosa".Microbiology Spectrum 11.1(2022).