Abstract
Pathogens differ in their host specificities, with species infecting a unique host (specialist pathogens) and others having a wide host range (generalists). Molecular determinants of pathogen's host range remain poorly understood. Secreted proteins of generalist pathogens are expected to have a broader range of intermolecular interactions (i.e., higher promiscuity) compared with their specialist counterparts. We hypothesize that this increased promiscuity of generalist secretomes may be based on an elevated content of primitive amino acids and intrinsically disordered regions, as these features are known to increase protein flexibility and interactivity. Here, we measure the proportion of primitive amino acids and percentage of intrinsically disordered residues in secreted, membrane, and cytoplasmic proteins from pathogens with different host specificity. Supporting our prediction, there is a significant general enrichment for primitive amino acids and intrinsically disordered regions in proteins from generalists compared to specialists, particularly among secreted proteins in prokaryotes. Our findings support our hypothesis that secreted proteins' amino acid composition and disordered content influence the pathogens' host range.
Highlights
Certain pathogens are highly species-specific, whereas others affect a broad range of hosts
We describe an enrichment of the secreted proteins of generalist pathogens in primitive amino acids and in intrinsically disordered regions
These features are known to increase protein flexibility and interactivity (Tompa et al, 2015; Ahrens et al, 2017), which may help generalist pathogens to interact with a broader range of hosts
Summary
Certain pathogens are highly species-specific, whereas others affect a broad range of hosts. Non-primitive amino acids have been correlated with lower solubility, enhanced rigidity, and highly structured conformations (Davidson et al, 1995; James & Tawfik, 2003; Doi et al, 2005). We hypothesize that, for an organism to be highly promiscuous or capable of infecting/interacting with multiple hosts, their secreted and membrane proteins should be enriched in primitive amino acids compared with secreted and membrane proteins of hostrestricted specialist pathogens. Primitive amino acids in surface exposed proteins might aid generalists’ ability to interact with a broader range of proteins from different hosts. Surface-exposed proteins from specialists do not require to interact with a high repertoire of proteins because they are host-restricted, and they might have a reduced amount of primitive amino acids
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