Resident Bacteria Contribute To Opportunistic Infections Of The Respiratory Tract

Author summaryThere is an urgent need for novel intervention strategies and techniques to address the increasing dissemination of multidrug-resistant Gram-negative bacterial pathogens. More importantly, secondary bacterial infections are common in clinical practice, whereas the growth dynamics of each individual in such coinfections are still complicated and elusive. In the current study, we first identified Staphylococcus spp., especially negligibly abundant S. chromogenes, facilitating the pathogenesis of Av. paragallinarum, a Gram-negative bacterium responsible for severe and acute avian respiratory disease worldwide. Furthermore, we developed therapeutic strategies using specific antibiotics against Staphylococcus spp. to relieve clinical symptoms and reduce Av. paragallinarum-associated infections in chickens. These results show that implementation of a proper intervention strategy can prevent opportunistic infections by regulating the microbiota and elucidate the development of alternative approaches for treating Gram-negative pathogenic bacterial infections.Opportunistic pathogens frequently cause volatile infections in hosts with compromised immune systems or a disrupted normal microbiota. The commensalism of diverse microorganisms contributes to colonization resistance, which prevents the expansion of opportunistic pathogens. Following microbiota disruption, pathogens promptly adapt to altered niches and obtain growth advantages. Nevertheless, whether and how resident bacteria modulate the growth dynamics of invasive pathogens and the eventual outcome of such infections are still unclear. Here, we utilized birds as a model animal and observed a resident bacterium exacerbating the invasion of Avibacterium paragallinarum (previously Haemophilus paragallinarum) in the respiratory tract. We first found that negligibly abundant Staphylococcus chromogenes, rather than Staphylococcus aureus, played a dominant role in Av. paragallinarum-associated infectious coryza in poultry based on epidemic investigations and in vitro analyses. Furthermore, we determined that S. chromogenes not only directly provides the necessary nutrition factor nicotinamide adenine dinucleotide (NAD(+)) but also accelerates its biosynthesis and release from host cells to promote the survival and growth of Av. paragallinarum. Last, we successfully intervened in Av. paragallinarum-associated infections in animal models using antibiotics that specifically target S. chromogenes. Our findings show that opportunistic pathogens can hijack commensal bacteria to initiate infection and expansion and suggest a new paradigm to ameliorate opportunistic infections by modulating the dynamics of resident bacteria.