Abstract
Pathogenic bacteria are a global health threat, with over 2 million infections caused by Gram-negative bacteria every year in the United States. This problem is exacerbated by the increase in resistance to common antibiotics that are routinely used to treat these infections, creating an urgent need for innovative ways to treat and prevent virulence caused by these pathogens. Many Gram-negative pathogenic bacteria use a type III secretion system (T3SS) to inject toxins and other effector proteins directly into host cells. The T3SS has become a popular anti-virulence target because it is required for pathogenesis and knockouts have attenuated virulence. It is also not required for survival, which should result in less selective pressure for resistance formation against T3SS inhibitors. In this review, we will highlight selected examples of direct antibody immunizations and the use of antibodies in immunotherapy treatments that target the bacterial T3SS. These examples include antibodies targeting the T3SS of Pseudomonas aeruginosa, Yersinia pestis, Escherichia coli, Salmonella enterica, Shigella spp., and Chlamydia trachomatis.
Highlights
The type III secretion system (T3SS) is a multimeric protein complex used by many pathogenic Gramnegative bacteria to cause and maintain an infection [1]
Due to the small diameter of the needle, the effector proteins must be unfolded to be translocated and are re-folded after entering the host cell [5]. These effector proteins are responsible for modifying the host cell functions in ways that are beneficial to the pathogen
Akopyan et al observed the presence of Yersinia outer proteins proteins (Yops) outside host cells and found that YopE is to the surface cells, but
Summary
The type III secretion system (T3SS) is a multimeric protein complex used by many pathogenic Gramnegative bacteria to cause and maintain an infection [1]. Due to the small diameter of the needle, the effector proteins must be unfolded to be translocated and are re-folded after entering the host cell [5]. Durand et al tested human colostrum for Abs against T3SS for Salmonella including the needle tip, translocon, and secreted effectors. They found that every sample collected spp., Shigella spp., and E. coli including the needle tip, translocon, and secreted effectors. They found contained to atcollected least onecontained of the aforementioned proteins. Antibody‐based treatments and prophylactics thatoftarget the T3SS of pathogenic bacteria
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