Co-operation during Staphylococcus aureus pathogenesis

Abstract

Introduction: Staphylococcus aureus is an invasive human pathogen associated with significant mortality. Host-pathogen dynamics during infection are poorly understood but recent work demonstrates that with high dose inocula, an immunological bottleneck allows clonal expansion of only a few bacteria, which go on to cause host damage. Methods: To interrogate this clonal phenomenon further, mixed strain inocula including varying ratios of virulent and either avirulent bacteria or bacterial cell components, were tested in the zebrafish embryo model of systemic infection. Results: The virulent strain S. aureus, SH1000 at high dose (1500 CFU) causes 50% embryo mortality. At low infective dose (150 CFU), S. aureus SH1000 is unable to cause significant mortality. Similarly, a high dose of either nonpathogenic bacterium such as Micrococcus luteus, attenuated S. aureusmutants or separated cell wall component, peptidoglycan, were unable to kill. However, when each of these was co-injected with the low infective dose of virulent S. aureus SH1000, significant mortality was observed. Discussion: Avirulent bacteria do not proliferate within the host, yet these so-called ‘bystanders’ permit low-dose S. aureus SH1000 to undergo clonal expansion and kill the host, far in excess of that seen when low dose is injected alone. Moreover, the essential cell wall component, peptidoglycan, was also able to augment killing of zebrafish embryos. Further analysis of this synergistic interaction may help us unravel mechanisms by which co-operation between bacteria affects pathogenesis. This has important clinical significance as a polymicrobial presence is likely to occur during human infection. http://dx.doi.org/10.1016/j.jinf.2015.09.021 IN TB PATIENTS FROM PERUVIAN SHANTYTOWNS, CATASTROPHIC COSTS EXPLAIN AS MANY ADVERSE TB OUTCOMES AS MDR TB Tom Wingfield , Marco Tovar , Rosario Montoya , Knut Lonnroth , Carlton Evans 1,3 1 Imperial College, London, UK 2 Innovation For Health And Development (IFHAD), London, UK Universidad Peruana Cayetano Heredia, Lima, Peru 4 Innovacion Por La Salud Y el Desarrollo (IPSYD), Lima, Peru World Health Organisation, TB Control Strategy, Geneva,