Abstract

Staphylococcus aureus is a pathogen that is the causative agent of several human and veterinary infections and plays a critical role in the clinical and subclinical mastitis of cattle. Autophagy is a conserved pathogen defence mechanism in eukaryotes. Studies have reported that S aureus can subvert autophagy and survive in cells. Staphylococcus aureus survival in cells is an important cause of chronic persistent mastitis infection. However, it is unclear whether S aureus can escape autophagy in innate immune cells. In this study, initiation of autophagy due to the presence of S aureus was detected in bovine macrophages. We observed autophagic vacuoles increased after S aureus infection of bovine macrophages by transmission electron microscopy (TEM). It was also found that S aureus‐infected bovine macrophages increased the expression of LC3 at different times(0, 0.5, 1, 1.5, 2, 2.5, 3 and 4 hours). Data also showed the accumulation of p62 induced by S aureus infection. Application of autophagy regulatory agents showed that the degradation of p62 was blocked in S aureus induced bovine macrophages. In addition, we also found that the accumulation of autophagosomes promotes S aureus to survive in macrophage cells. In conclusion, this study indicates that autophagy occurs in S aureus‐infected bovine macrophages but is blocked at a later stage of autophagy. The accumulation of autophagosomes facilitates the survival of S aureus in bovine macrophages. These findings provide new insights into the interaction of S aureus with autophagy in bovine macrophages.

Highlights

  • Mastitis results in low milk production and poor milk quality, causing significant economic loss to the dairy industry.[1,2] Bovine mastitis is divided into clinical and subclinical mastitis, and the incidence of subclinical mastitis is much higher than that of clinical mastitis.[3,4] mastitis is caused by several pathogens, Staphylococcus aureus intramammary infection (IMI) is the mainCai and Li contributed to this work.| 3460 wileyonlinelibrary.com/j ournal/jcmmJ Cell Mol Med. 2020;24:3460–3468.| 3461 cause of subclinical mastitis

  • We aimed to reveal whether the autophagic flux is unobstructed in S aureus-infected bovine macrophages, and the relationship between the patency of autophagic flux and the intracellular survival of S aureus

  • We demonstrate for the first time that S aureus can block autophagic flux and promote its survival in bovine macrophages

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Summary

Introduction

Staphylococcus aureus, originally thought to be an extracellular pathogen, has been shown to invade various types of professional and non-professional phagocytic cells and may be a facultative intracellular pathogen.[5,6,7,8,9]. A fundamental cellular homeostatic mechanism, is an intracellular degradation/recycling system in eukaryotic cells and transports damaged cytoplasm and organelles to lysosomes for degradation. Effective autophagy is dependent on the balance between autophagosome formation and elimination, and any defects in the autophagy pathway can cause autophagy dysfunction. There is substantial evidence showing that autophagy dysregulation can lead to mammalian diseases.[10,11,12]

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