Nutrient Limitation Governs Staphylococcus aureus Metabolism and Niche Adaptation in the Human Nose

Abstract

Colonization of the human nose by Staphylococcus aureus in one-third of the population represents a major risk factor for invasive infections. The basis for adaptation of S. aureus to this specific habitat and reasons for the human predisposition to become colonized have remained largely unknown. Human nasal secretions were analyzed by metabolomics and found to contain potential nutrients in rather low amounts. No significant differences were found between S. aureus carriers and non-carriers, indicating that carriage is not associated with individual differences in nutrient supply. A synthetic nasal medium (SNM3) was composed based on the metabolomics data that permits consistent growth of S. aureus isolates. Key genes were expressed in SNM3 in a similar way as in the human nose, indicating that SNM3 represents a suitable surrogate environment for in vitro simulation studies. While the majority of S. aureus strains grew well in SNM3, most of the tested coagulase-negative staphylococci (CoNS) had major problems to multiply in SNM3 supporting the notion that CoNS are less well adapted to the nose and colonize preferentially the human skin. Global gene expression analysis revealed that, during growth in SNM3, S. aureus depends heavily on de novo synthesis of methionine. Accordingly, the methionine-biosynthesis enzyme cysteine-γ-synthase (MetI) was indispensable for growth in SNM3, and the MetI inhibitor DL-propargylglycine inhibited S. aureus growth in SNM3 but not in the presence of methionine. Of note, metI was strongly up-regulated by S. aureus in human noses, and metI mutants were strongly abrogated in their capacity to colonize the noses of cotton rats. These findings indicate that the methionine biosynthetic pathway may include promising antimicrobial targets that have previously remained unrecognized. Hence, exploring the environmental conditions facultative pathogens are exposed to during colonization can be useful for understanding niche adaptation and identifying targets for new antimicrobial strategies.

Increased airway glucose increases airway bacterial load in hyperglycaemia

“…Glucose is not the only nutrient that is restricted in the airways, levels of amino acids and other carbon sources are also limited22. Interactions and competition between microbes for this limited resource can lead to altered virulence of the bacteria23.…”

The biogeography of polymicrobial infection

“…This bacterial genus is prevalent on human skin 119 , but in contrast to many other staphylococci, Staphylococcus aureus also persistently colonizes one-third of human nasal cavities 120 . Supporting a nutritional basis for this pattern, S. aureus , but not skin-restricted staphylococci, can sustain growth in a synthetic nasal medium 121 . These experiments have revealed that the acquisition of a specific nutrient, methionine, is a key trait required for S. aureus to colonize the nose (see the figure).…”

Branching Out: Alterations in Bacterial Physiology and Virulence Due to Branched-Chain Amino Acid Deprivation

“…aureus growth in vivo remains to be determined, although biosynthesis likely plays a role in maintaining BCAA levels, as the biosynthetic genes are upregulated when S. aureus is grown in blood, the lung environment, and in nasal secretions (131–133). In S.…”