The blp Locus of Streptococcus pneumoniae Plays a Limited Role in the Selection of Strains That Can Cocolonize the Human Nasopharynx.
Nasopharyngeal colonization is important for Streptococcus pneumoniae evolution, providing the opportunity for horizontal gene transfer when multiple strains co-occur. Although colonization with more than one strain of pneumococcus is common, the factors that influence the ability of strains to coexist are not known. A highly variable blp (bacteriocin-like peptide) locus has been identified in all sequenced strains of S. pneumoniae This locus controls the regulation and secretion of bacteriocins, small peptides that target other bacteria. In this study, we analyzed a series of cocolonizing isolates to evaluate the impact of the blp locus on human colonization to determine whether competitive phenotypes of bacteriocin secretion restrict cocolonization. We identified a collection of 135 nasopharyngeal samples cocolonized with two or more strains, totaling 285 isolates. The blp locus of all strains was characterized genetically with regard to pheromone type, bacteriocin/immunity content, and potential for locus functionality. Inhibitory phenotypes of bacteriocin secretion and locus activity were assessed through overlay assays. Isolates from single colonizations (n = 298) were characterized for comparison. Cocolonizing strains had a high diversity of blp cassettes; approximately one-third displayed an inhibitory phenotype in vitro Despite in vitro evidence of competition, pneumococci cocolonized the subjects independently of blp pheromone type (P = 0.577), bacteriocin/immunity content, blp locus activity (P = 0.798), and inhibitory phenotype (P = 0.716). In addition, no significant differences were observed when single and cocolonizing strains were compared. Despite clear evidence of blp-mediated competition in experimental models, the results of our study suggest that the blp locus plays a limited role in restricting pneumococcal cocolonization in humans.



Nasopharyngeal colonization with Streptococcus pneumoniae (pneumococcus) is important for pneumococcal evolution, as the nasopharynx represents the major site for horizontal gene transfer when multiple strains co-occur, a phenomenon known as cocolonization. Understanding how pneumococcal strains interact within the competitive environment of the nasopharynx is of chief importance in the context of pneumococcal ecology. In this study, we used an unbiased collection of naturally co-occurring pneumococcal strains and showed that a biological process frequently used by bacteria for competition-bacteriocin production-is not decisive in the coexistence of pneumococci in the host, in contrast to what has been shown in experimental models.
Laboratory of Molecular Microbiology of Human Pathogens, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal.
Carina
C
Valente
Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan, USA Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA.
Suzanne
S
Dawid
BioISI-Biosystems & Integrative Sciences Institute, Faculdade de Ciências da Universidade de Lisboa, Lisbon, Portugal.
Francisco R
FR
Pinto
Institute for Infection and Immunity, St. George's, University of London, London, United Kingdom BUGS Bioscience, London Bioscience Innovation Centre, London, United Kingdom.
Jason
J
Hinds
Laboratory of Molecular Microbiology of Human Pathogens, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal.
Alexandra S
AS
Simões
Institute for Infection and Immunity, St. George's, University of London, London, United Kingdom BUGS Bioscience, London Bioscience Innovation Centre, London, United Kingdom.
Katherine A
KA
Gould
Laboratory of Molecular Microbiology of Human Pathogens, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal.
Luís A
LA
Mendes
Laboratory of Molecular Genetics, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal Laboratory of Microbiology and Infectious Diseases, The Rockefeller University, New York, New York, USA.
Hermínia
H
de Lencastre
Laboratory of Molecular Microbiology of Human Pathogens, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal rsaleao@itqb.unl.pt.
Raquel
R
Sá-Leão
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D009305:Nasopharynx / Q000382:microbiology*; D011008:Pneumococcal Infections / Q000382:microbiology*; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000254:growth & development* / Q000302:isolation & purification / Q000378:metabolism*
D001426:Bacterial Proteins