Unraveling the role of UilS, a urea-induced acyl-homoserine lactonase that enhances Serratia marcescens fitness, interbacterial competition, and urinary tract infection.

Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 101519231 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2150-7511 (Electronic) NLM ISO Abbreviation: mBio Subsets: MEDLINE

Original Publication: Washington, D.C. : American Society for Microbiology

Serratia marcescens*/genetics ; Serratia marcescens*/enzymology ; Serratia marcescens*/drug effects ; Serratia marcescens*/physiology ; Urinary Tract Infections*/microbiology ; Urea*/pharmacology ; Urea*/metabolism ; Serratia Infections*/microbiology ; Quorum Sensing*; Animals ; Mice ; Humans ; Carboxylic Ester Hydrolases/genetics ; Carboxylic Ester Hydrolases/metabolism ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Gene Expression Regulation, Bacterial ; Pseudomonas aeruginosa/genetics ; Pseudomonas aeruginosa/drug effects ; Pseudomonas aeruginosa/enzymology ; Female ; Acyl-Butyrolactones/metabolism ; Microbial Interactions

Serratia marcescens , a member of the Enterobacteriaceae family, is an opportunistic human pathogen and a frequent cause of urinary tract infections. Clinical isolates often exhibit resistance to multiple antibiotics, posing challenges for successful treatment. Understanding its pathogenic mechanisms is crucial for elucidating new potential targets to develop effective therapeutic interventions and manage S. marcescens infections. This work identifies u rea- i nduced l actonase of S erratia (UilS), a lactonase encoded in the S. marcescens RM66262 strain isolated from a patient with a urinary tract infection. The study explores the bacterium's response to urea, a major component of urine, and its impact on uilS expression. We found that UilS degrades acyl-homoserine lactones (AHL) autoinducers traditionally associated with quorum sensing mechanisms. Surprisingly, UilS is able to degrade self and non-self AHL, exhibiting quorum-quenching activity toward Pseudomonas aeruginosa . We found that LuxR regulates uilS expression that is enhanced in the presence of AHL. In addition, urea-dependent induction of UilS expression is controlled by the transcriptional response regulator CpxR. UilS confers fitness advantage to S. marcescens , especially in the presence of urea, emphasizing the adaptive plasticity of strains to modulate gene expression based on environmental signals and population density. We also discovered a novel bacterial killing capacity of S. marcescens that involves UilS, indicating its importance in the interspecies interaction of Serratia . Finally, we found that a uilS mutant strain displays attenuated colonization in a mouse model of catheter-associated urinary tract infection. uilS is present in clinical but absent in environmental isolates, suggesting an evolutionary adaptation to host-specific selective pressures.
Importance: This work reveals the acyl-homoserine lactonase u rea- i nduced l actonase of S erratia as a novel virulence factor of Serratia marcescens , unraveling a potential target to develop antimicrobial strategies and shedding light on the complex regulatory network governing pathogenicity and adaptation to host environments.
Competing Interests: The authors declare no conflict of interest.

J Bacteriol. 2012 Jun;194(11):2949-61. (PMID: 22467788)
Bioinformatics. 2010 Mar 1;26(5):589-95. (PMID: 20080505)
Nat Rev Microbiol. 2016 Aug 11;14(9):576-88. (PMID: 27510864)
FEMS Microbiol Lett. 2007 Jan;266(1):1-9. (PMID: 17233715)
PLoS One. 2017 Mar 22;12(3):e0174454. (PMID: 28328989)
J Bacteriol. 1996 Jan;178(2):435-40. (PMID: 8550463)
BMC Genomics. 2008 Feb 08;9:75. (PMID: 18261238)
Microbiology (Reading). 2006 Feb;152(Pt 2):485-491. (PMID: 16436436)
Expert Rev Anti Infect Ther. 2020 Dec;18(12):1221-1233. (PMID: 32749905)
PLoS One. 2011;6(8):e23314. (PMID: 21876746)
Genome Announc. 2015 Dec 03;3(6):. (PMID: 26634764)
J Bacteriol. 2011 Jan;193(1):63-74. (PMID: 20971912)
FEMS Microbiol Lett. 2008 Feb;279(1):124-30. (PMID: 18177311)
J Bacteriol. 2008 Jan;190(1):213-20. (PMID: 17981971)
mBio. 2017 Aug 22;8(4):. (PMID: 28830939)
Infect Immun. 2021 Jul 15;89(8):e0011121. (PMID: 33820815)
Mol Plant Microbe Interact. 1998 Nov;11(11):1119-29. (PMID: 9805399)
Indian J Microbiol. 2014 Jun;54(2):158-62. (PMID: 25320416)
J Bacteriol. 2018 Mar 26;200(8):. (PMID: 29378892)
Bioinformatics. 2014 Apr 1;30(7):923-30. (PMID: 24227677)
J Biol Chem. 2023 Sep;299(9):105119. (PMID: 37527778)
Mol Plant Microbe Interact. 2000 Nov;13(11):1243-50. (PMID: 11059491)
PeerJ. 2023 Jan 5;11:e14399. (PMID: 36627920)
J Biosci. 2020;45:. (PMID: 32020908)
Int J Med Microbiol. 2010 Jun;300(5):304-12. (PMID: 20347390)
PLoS Pathog. 2011 Nov;7(11):e1002386. (PMID: 22102820)
J Clin Diagn Res. 2013 Feb;7(2):243-6. (PMID: 23543704)
Sci Rep. 2019 Dec 27;9(1):20159. (PMID: 31882896)
Bioinformatics. 2014 Aug 1;30(15):2114-20. (PMID: 24695404)
Genome Biol. 2014;15(12):550. (PMID: 25516281)
J Bacteriol. 1995 Nov;177(22):6381-9. (PMID: 7592412)
Mol Microbiol. 2002 Sep;45(6):1655-71. (PMID: 12354232)
J Bacteriol. 1988 Sep;170(9):4141-6. (PMID: 2842305)
Nat Rev Microbiol. 2019 Jun;17(6):371-382. (PMID: 30944413)
Mol Biol Evol. 2014 May;31(5):1077-88. (PMID: 24600054)
Microbiol Mol Biol Rev. 2015 Mar;79(1):153-69. (PMID: 25694124)
Mol Microbiol. 2023 Mar;119(3):326-339. (PMID: 36627840)
FEMS Microbiol Rev. 2007 Jul;31(4):407-24. (PMID: 17459113)
Sci Rep. 2018 Aug 14;8(1):12157. (PMID: 30108246)
J Vis Exp. 2015 Jun 23;(100):e52892. (PMID: 26132341)
Philos Trans R Soc Lond B Biol Sci. 2015 Oct 5;370(1679):. (PMID: 26370934)
J Hosp Infect. 2023 Oct;140:124-131. (PMID: 37562591)
J Bacteriol. 1997 Aug;179(15):4754-60. (PMID: 9244262)
Infect Immun. 2014 Sep;82(9):3542-54. (PMID: 24914224)
Methods Enzymol. 2002;358:452-84. (PMID: 12474406)
Appl Environ Microbiol. 2007 Oct;73(20):6339-44. (PMID: 17675425)
Nat Biotechnol. 2011 Jan;29(1):24-6. (PMID: 21221095)
FEMS Microbiol Rev. 2016 Jan;40(1):86-116. (PMID: 26432822)
J Bacteriol. 2005 May;187(10):3477-85. (PMID: 15866935)
Nat Commun. 2019 Jun 24;10(1):2763. (PMID: 31235751)
Infect Immun. 2010 Oct;78(10):4166-75. (PMID: 20696830)
FEMS Microbiol Lett. 2012 Jan;326(1):2-11. (PMID: 22092948)
Front Microbiol. 2018 Jan 15;8:2689. (PMID: 29379483)
Gene. 1991 Jun 15;102(1):75-8. (PMID: 1840539)
Gene. 1991 Dec 20;109(1):137-41. (PMID: 1756974)
Infect Immun. 2015 Jul;83(7):2907-16. (PMID: 25939509)
Biotechniques. 1999 May;26(5):824-6, 828. (PMID: 10337469)
Res Microbiol. 2017 Jul - Aug;168(6):567-574. (PMID: 28366837)
Genome Biol Evol. 2019 Mar 1;11(3):931-936. (PMID: 30840067)
Mol Microbiol. 1996 Apr;20(1):127-36. (PMID: 8861211)
Nucleic Acids Res. 1986 Jul 25;14(14):5843-55. (PMID: 3016665)

PICT 2019-00492 MINCyT | Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT)

Keywords: Serratia marsescens; bacterial virulence; lactonase; pathogenesis; quorum quenching

8W8T17847W (Urea)
EC 3.1.1.- (Carboxylic Ester Hydrolases)
0 (Bacterial Proteins)
EC 3.1.1.- (N-acyl homoserine lactonase)
0 (Acyl-Butyrolactones)

Date Created: 20241030 Date Completed: 20241211 Latest Revision: 20241213

20241213

PMC11633161

10.1128/mbio.02505-24

39475236