Staphylococcus aureus is a mammalian commensal and opportunistic pathogen that colonizes niches such as skin, nares and diverse mucosal membranes of about 20-30% of the human population. S. aureus can cause a wide spectrum of diseases in humans and both methicillin-sensitive and methicillin-resistant strains are common causes of nosocomial- and community-acquired infections. Despite the prevalence of literature characterising staphylococcal pathogenesis in humans, S. aureus is a major cause of infection and disease in a plethora of animal hosts leading to a significant impact on public health and agriculture. Infections in animals are deleterious to animal health, and animals can act as a reservoir for staphylococcal transmission to humans. Host-switching events between humans and animals and amongst animals are frequent and have been accentuated with the domestication and/or commercialisation of specific animal species. Host-switching is typically followed by subsequent adaptation through acquisition and/or loss of mobile genetic elements such as phages, pathogenicity islands and plasmids as well as further host-specific mutations allowing it to expand into new host populations. In this chapter, we will be giving an overview of S. aureus in animals, how this bacterial species was, and is, being transferred to new host species and the key elements thought to be involved in its adaptation to new ecological host niches. We will also highlight animal hosts as a reservoir for the development and transfer of antimicrobial resistance determinants.

Sinorhizobium meliloti differentiates into persisting, nitrogen-fixing bacteroids within root nodules of the legume Medicago truncatula. Nodule-specific cysteine-rich antimicrobial peptides (NCR AMPs) and the bacterial BacA protein are essential for bacteroid development. However, the bacterial factors central to the NCR AMP response and the in planta role of BacA are unknown. We investigated the hypothesis that BacA is critical for the bacterial response towards NCR AMPs. We found that BacA was not essential for NCR AMPs to induce features of S. meliloti bacteroids in vitro. Instead, BacA was critical to reduce the amount of NCR AMP-induced membrane permeabilization and bacterial killing in vitro. Within M. truncatula, both wild-type and BacA-deficient mutant bacteria were challenged with NCR AMPs, but this resulted in persistence of the wild-type bacteria and rapid cell death of the mutant bacteria. In contrast, BacA was dispensable for bacterial survival in an M. truncatula dnf1 mutant defective in NCR AMP transport to the bacterial compartment. Therefore, BacA is critical for the legume symbiosis by protecting S. meliloti against the bactericidal effects of NCR AMPs. Host AMPs are ubiquitous in nature and BacA proteins are essential for other chronic host infections by symbiotic and pathogenic bacteria. Hence, our findings suggest that BacA-mediated protection of bacteria against host AMPs is a critical stage in the establishment of different prolonged host infections. Certain bacterial species have the unique capacity to enter into eukaryotic host cells and establish prolonged infections, which can be beneficial (e.g. bacterial-legume symbiosis) or detrimental (e.g. chronic disease) for the host. However, the mechanisms by which bacteria persist in host cells are poorly understood. Legume peptides and the bacterial BacA membrane protein play essential roles in enabling bacteria to establish prolonged legume infections. However, the biological function of BacA in persistent legume infections has eluded scientists for nearly two decades. In this article, we investigated a potential relationship between legume peptides and BacA in the establishment of prolonged bacterial-legume infections. We found that BacA was critical to protect bacteria against the antimicrobial action of legume peptides, thereby allowing the peptides to induce bacterial persistence within the legume rather than rapid bacterial death. Mammalian hosts also produce peptides in response to invading microorganisms and BacA proteins are critical for medically important bacterial pathogens such as Mycobacterium tuberculosis to form prolonged mammalian infections. Therefore, our results suggest that BacA-mediated protection against host peptides might be a conserved mechanism used by both symbiotic and pathogenic bacterial species to establish long-term host infections.

Rhizobia differentiate from free-living soil bacteria to nitrogen fixing endosymbionts of legume plants requiring specific adaptations for chronic maintenance.

It is commonly assumed that the horizontal transfer of most bacterial chromosomal genes is limited, in contrast to the frequent transfer observed for typical mobile genetic elements. However, this view has been recently challenged by the discovery of lateral transduction in Staphylococcus aureus, where temperate phages can drive the transfer of large chromosomal regions at extremely high frequencies. Here, we analyse previously published as well as new datasets to compare horizontal gene transfer rates mediated by different mechanisms in S. aureus and Salmonella enterica. We find that the horizontal transfer of core chromosomal genes via lateral transduction can be more efficient than the transfer of classical mobile genetic elements via conjugation or generalized transduction. These results raise questions about our definition of mobile genetic elements, and the potential roles played by lateral transduction in bacterial evolution.

The root nodules of certain legumes including Medicago truncatula produce >300 different nodule-specific cysteine-rich (NCR) peptides. Medicago NCR antimicrobial peptides (AMPs) mediate the differentiation of the bacterium, Sinorhizobium meliloti into a nitrogen-fixing bacteroid within the legume root nodules. In vitro, NCR AMPs such as NCR247 induced bacteroid features and exhibited antimicrobial activity against S. meliloti. The bacterial BacA protein is critical to prevent S. meliloti from being hypersensitive toward NCR AMPs. NCR AMPs are cationic and have conserved cysteine residues, which form disulfide (S–S) bridges. However, the natural configuration of NCR AMP S–S bridges and the role of these in the activity of the peptide are unknown. In this study, we found that either cysteine replacements or S–S bond modifications influenced the activity of NCR247 against S. meliloti. Specifically, either substitution of cysteines for serines, changing the S–S bridges from cysteines 1–2, 3–4 to 1–3, 2–4 or oxidation of NCR247 lowered its activity against S. meliloti. We also determined that BacA specifically protected S. meliloti against oxidized NCR247. Due to the large number of different NCRs synthesized by legume root nodules and the importance of bacterial BacA proteins for prolonged host infections, these findings have important implications for analyzing the function of these novel peptides and the protective role of BacA in the bacterial response toward these peptides.