The Ami-AliA/AliB Permease of Streptococcus pneumoniae Is Involved in Nasopharyngeal Colonization but Not in Invasive Disease

Abstract

The Ami-AliA/AliB oligopeptide permease is an ATP-binding cassette transporter which is found in Streptococcus pneumoniae and which is involved in nutrient uptake. We investigated the role of the three paralogous oligopeptide-binding lipoproteins AmiA, AliA, and AliB by using murine models of pneumococcal colonization and invasive disease. A series of mutants lacking aliA, aliB, and amiA either alone or in combination as double or triple mutations were used. Inoculation of the nasopharynx with a mixture of the obl (oligopeptide-binding lipoprotein-negative) triple-mutant and wild-type (D39) bacteria resulted in significantly smaller numbers of obl bacteria colonizing the nasopharynx. The use of a mixture of individual mutants and wild-type pneumococci revealed that AmiA, AliA, and AliB were all required for successful colonization of the nasopharynx. The obl mutant was more attenuated than the aliB mutant but not the aliA or amiA mutant. Therefore, there is some redundancy in the Ami-AliA/AliB complex in terms of nasopharyngeal colonization, with AliA and AmiA being able to compensate for the removal of AliB. Animals with invasive disease caused by these mutants had survival times, bacterial loads, and inflammatory cytokine production levels similar to those of animals infected with wild-type pneumococci. Our results show that although the Ami-AliA/AliB complex is not required for virulence during pneumococcal pneumonia, it does play a role in colonization of the nasopharynx.

Site-Specific Contributions of Glutamine-Dependent Regulator GlnR and GlnR-Regulated Genes to Virulence of Streptococcus pneumoniae

“…Many studies have shown that expression of pneumococcal proteins during pathogenesis is required at different stages of infection (15,21,25). One study, performed by Oggioni and coworkers, presents evidence that the "transcriptional state" of the pneumococcal cells differs at particular niches within the host (24).…”

“…Nine-week-old female outbred CD-1 mice (Harlan, Horst, Netherlands) were used for all infection models. Prior to the infection experiments, D39 wild-type and mutant strains were passaged in mice as described previously (15). Cultures of mouse-passaged S. pneumoniae strains were grown to an optical density at 600 nm of 0.3 and stored in aliquots at Ϫ80°C in 10% glycerol.…”

“…Infection models were essentially performed as described previously (9,10,15). Nine-week-old female outbred CD-1 mice (Harlan, Horst, Netherlands) were used for all infection models.…”

“…In line with this, several systems involved in nutrition and metabolism have been suggested to be important for virulence. For example, PsaA is part of an Mn(II) uptake system and contributes to colonization and invasive disease (2,13) while the Ami-AliA/ AliB oligopeptide uptake system contributes to colonization only (15).…”

Variation in the Presence of Neuraminidase Genes among Streptococcus pneumoniae Isolates with Identical Sequence Types

“…Signature-tagged mutagenesis has identified putative virulence factors specific for pneumonia (33) and for colonization of mucosal surfaces (18). An ATP-binding cassette transporter, the Ami-AliA/AliB permease, has been shown to be important for colonization and not invasive disease in a mouse model of infection (22). In addition to tissuespecific virulence factors, new research indicates that specific virulence factors are important for transition between tissue sites (29).…”