The Impact of Intraspecies and Interspecies Bacterial Interactions on Disease Outcome

Abstract

The human microbiota is an array of microorganisms known to interact with the host and other microbes. These interactions can be competitive, as microbes must adapt to host- and microorganism-related stressors, thus producing toxic molecules, or cooperative, whereby microbes survive by maintaining homeostasis with the host and host-associated microbial communities. As a result, these microbial interactions shape host health and can potentially result in disease. In this review, we discuss these varying interactions across microbial species, their positive and negative effects, the therapeutic potential of these interactions, and their implications on our knowledge of human well-being.

Keywords: bacterial interactions; commensal; host–pathogen interface; pathogen; polymicrobial infection.

Figure 1

Quorum sensing-mediated intraspecies interactions in bacteria can elevate pathogenesis in host tissues. AHL-bound autoinducers in Gram-negative bacteria like P. aeruginosa can promote the expression of several virulence factors such as rhamnolipids, pyocyanin, and other biofilm-associated genes. Some of these factors can target host immune cells such as macrophages upon phagocytosis. Similarly, QS-mediated biofilm-associated genes can prevent the elimination of pathogenic cells from host tissues by resisting antibiotic effects of antimicrobial peptides, antibiotic drugs, and phagocytic immune cells. Additionally, QS-induced virulence factors including proteases produced by Gram-positive bacteria, such as S. aureus, can degrade immune system cells upon infection.

Figure 2

Intraspecies interactions can alleviate pathogenesis in host tissues. E. coli Nissle 1917 strain outcompetes enterohaemorrhagic and enteropathogenic E. coli by forming highly robust biofilms and reducing the colonizing area for the latter in host tissues (top panel). Non-toxigenic B. fragilis strains colonizing the gut use their T6SS to lyse enterotoxigenic B. fragilis and limit colonization of the pathogenic strain (middle panel). In CF lungs, R pyocin producing P. aeruginosa strains can inhibit S pyocin producing ones by targeting biofilm communities of the latter (bottom panel). Created with BioRender.com.

Figure 3

Interspecies interactions can elevate pathogenesis in host tissues. (A). In inner ear infections such as otitis media, causative pathogen M. catarrhalis produces β-lactamase which protects S. pneumoniae from host antibacterial molecules. An increase in the cell density of S. pneumoniae, in turn, leads to increased production of auto-inducer AI-2 (via QS) and increases colonization of M. catarrhalis. This positive feedback loop contributes to increased antibacterial resistance in pathogenic microorganisms. (B). In the oral cavity, A. actinomycetemcomitans secrete cytoplasmic catalases that convert H₂O₂ produced by S. sanguinis to non-lethal end-products and protects pathogenic species, P. gingivalis, from the effects of reactive oxygen species. (C). In the infected CF lung, reduction in the expression of anti-staphylococcal factors secreted by P. aeruginosa and production of molecules such as α-toxins that can counteract the host defenses by S. aureus can lead to increased survival of both the pathogenic species. (D). In the GI tract, presence of B. thetaiotaomicron, a symbiotic bacterial species which produces sialic acids, helps pathogenic C. difficile to colonize and grow in the gut by utilizing the acids as a nutrient source. Created with BioRender.com.

Figure 4

Interspecies interactions can alleviate pathogenesis in host tissues. (A). Commensal microorganisms, including E. coli Nissle 1917, can outcompete growth of pathogenic bacteria such as S. typhimurium via competitive iron acquisition in the human gut. Such mechanisms exhibited by non-pathogenic microbes help in alleviating pathogenesis of the human host. (B). Antibiotic peptide, lugdunin, produced by S. lugdunensis, a resident bacterial species, inhibits colonization of S. aureus in the human nasal cavity. (C). In CF lung, non-pathogenic B. thailandensis cells target B. multivorans by delivering toxins via T6SS contact-dependent growth inhibition, thereby killing the pathogenic species. Created with BioRender.com.