title: Deletion analysis of Streptococcus pneumoniae late competence genes distinguishes virulence determinants that are dependent or independent of competence induction.
abstract: The competence regulon of Streptococcus pneumoniae (pneumococcus) is crucial for genetic transformation. During competence development, the alternative sigma factor ComX is activated, which in turn, initiates transcription of 80 'late' competence genes. Interestingly, only 16 late genes are essential for genetic transformation. We hypothesized that these late genes that are dispensable for competence are beneficial to pneumococcal fitness during infection. These late genes were systematically deleted, and the resulting mutants were examined for their fitness during mouse models of bacteremia and acute pneumonia. Among these, 14 late genes were important for fitness in mice. Significantly, deletion of some late genes attenuated pneumococcal fitness to the same level in both wild-type and ComX-null genetic backgrounds, suggesting that the constitutive baseline expression of these genes was important for bacterial fitness. In contrast, some mutants were attenuated only in the wild-type genetic background but not in the ComX-null background, suggesting that specific expression of these genes during competence state contributed to pneumococcal fitness. Increased virulence during competence state was partially caused by the induction of allolytic enzymes that enhanced pneumolysin release. These results distinguish the role of basal expression versus competence induction in virulence functions encoded by ComX-regulated late competence genes.
authors.affiliation: Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
authors.forename: Luchang
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
authors.forename: Jingjun
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
authors.forename: Zhizhou
authors.initials: Z
authors.lastname: Kuang
authors.affiliation: Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Vidal
authors.affiliation: Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
authors.forename: Gee W
authors.initials: GW
authors.lastname: Lau
mesh_terms: D000818:Animals; D016470:Bacteremia / Q000382:microbiology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D061269:DNA Transformation Competence / Q000235:genetics*; D004195:Disease Models, Animal; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D056084:Genetic Fitness; D051379:Mice; D009154:Mutation; D011008:Pneumococcal Infections / Q000382:microbiology*; D011018:Pneumonia, Pneumococcal / Q000382:microbiology; D018085:Regulon; D013296:Streptococcus pneumoniae / Q000235:genetics* / Q000472:pathogenicity*; D013301:Streptolysins / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014774:Virulence / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; C120829:ComX protein, Streptococcus; D013301:Streptolysins; D014157:Transcription Factors; C032290:plY protein, Streptococcus pneumoniae
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