Anaerobiosis, a neglected factor in phage-bacteria interactions

Abstract

ABSTRACT Phage therapy is a promising alternative in treating bacterial infections; however, understanding how bacteria and phages interact according to the environment is crucial. Although most phage therapy applications are intended for anaerobic environments (such as intestine or wounds), research on the effects of oxygen absence on the phage infection process is scarce . Here, we studied the effect of anoxic conditions in a Salmonella sp. – phage model, given the prevalence of this bacterial pathogen in anaerobic environments, and the potential of phage therapy for its control. Our results show that oxygen-deprived conditions affect the life cycle length of the phage and its capacity to control the bacterial population. Changes in host cell size associated with the FtsZ protein were observed, along with a modified emergence of resistance against the phage under different oxygen conditions. Interestingly, transcriptomic analyses revealed that phage infection in aerobic conditions triggers the expression of genes associated with nitrate reduction, an alternative pathway for anaerobic respiration. Meanwhile, uninfected anaerobic cultures displayed the upregulation of genes involved in a different anaerobic metabolic route comprising the transport of thiosulfate and sulfate. Altogether, our results provide insights into the importance of considering oxygen availability as an important factor for phage therapy when working with facultative anaerobic bacteria. IMPORTANCE Many parameters affect phage-bacteria interaction. Some of these parameters depend on the environment in which the bacteria are present. Anaerobiosis effect on phage infection in facultative anaerobic bacteria has not yet been studied. The absence of oxygen triggers metabolic changes in facultative bacteria and this affects phage infection and viral life cycle. Understanding how an anaerobic environment can alter the behavior of phages during infection is relevant for the phage therapy success.