Wu Yifan, Wang Yongqiang, Yang Huiming, Li Qian, Gong Xiaoxia, Zhang Guozhong, Zhu Kui
National Center for Veterinary Drug Safety Evaluation, College of Veterinary Medicine, China Agricultural University, Beijing, China.
Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China.
PLoS Pathog. 2021 Mar 19;17(3):e1009436. doi: 10.1371/journal.ppat.1009436. eCollection 2021 Mar.
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.
机会性病原体经常在免疫系统受损或正常微生物群被破坏的宿主中引起易变的感染。多种微生物的共生有助于形成定植抗性,从而防止机会性病原体的扩张。在微生物群被破坏后,病原体迅速适应改变的生态位并获得生长优势。然而,常驻细菌是否以及如何调节侵入性病原体的生长动态以及此类感染的最终结果仍不清楚。在这里,我们以鸟类为模型动物,观察到一种常驻细菌加剧了副鸡禽杆菌(以前称为副鸡嗜血杆菌)在呼吸道中的入侵。我们首先发现,基于流行病学调查和体外分析,在禽类副鸡禽杆菌相关的传染性鼻炎中,极低丰度的产色葡萄球菌而非金黄色葡萄球菌起主导作用。此外,我们确定产色葡萄球菌不仅直接提供必需的营养因子烟酰胺腺嘌呤二核苷酸(NAD+),还加速其生物合成并从宿主细胞中释放,以促进副鸡禽杆菌的存活和生长。最后,我们使用特异性靶向产色葡萄球菌的抗生素成功干预了动物模型中副鸡禽杆菌相关的感染。我们的研究结果表明,机会性病原体可以劫持共生细菌来引发感染和扩张,并提出了一种通过调节常驻细菌的动态来改善机会性感染的新范式。