**Julia A. Hotinger and Aaron E. May \***

Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23219, USA; hotingerja@vcu.edu

**\*** Correspondence: aemay@vcu.edu; Tel.: +1-804-828-7134

Received: 10 June 2020; Accepted: 22 July 2020; Published: 27 July 2020

**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*.

**Keywords:** type III secretion system; antibodies; prophylaxis; antibacterials; antibiotics
