Vibrio cholerae is a natural inhabitant of aquatic ecosystems worldwide, typically residing in coastal or brackish water. While more than 200 serogroups have been identified, only serogroups O1 and O139 have been associated with epidemic cholera. However, infections other than cholera can be caused by nonepidemic, non-O1/non-O139 V. cholerae strains, including gastroenteritis and extraintestinal infections. While V. cholerae can also survive in freshwater, that is typically only observed in regions of the world where cholera is endemic. We recently isolated V. cholerae from several locations in lakes and rivers in northwest Ohio. These isolates were all found to be non-O1/non-O139 V. cholerae strains, that would not cause cholera. However, these isolates contained a variety of virulence genes, including ctxA, rtxA, rtxC, hlyA, and ompU. Therefore, it is possible that some of these isolates have the potential to cause gastroenteritis or other infections in humans. We also investigated the relative motility of the isolates and their ability to form biofilms as this is important for V. cholerae survival in the environment. We identified one isolate that forms very robust biofilms, up to 4x that of our laboratory strains. Finally, we investigated the susceptibility of these isolates to a panel of antibiotics. We found that many of the isolates showed decreased susceptibility to some of the antibiotics tested, which could be of concern. While we do not know if these isolates are pathogenic to humans, increased surveillance to better understand the public health risk to the local community should be considered.

The phage shock protein (Psp) system is a stress response pathway that senses and responds to inner membrane damage. The genetic components of the Psp system are present in several clinically relevant Gram-negative bacteria, includingVibrio cholerae. However, most of the current knowledge about the Psp response stems fromin vitrostudies inEscherichia coliandYersinia enterocolitica. In fact, the Psp response inV. choleraehas remained completely uncharacterized. In this study, we demonstrate thatV. choleraedoes have a functional Psp response system. We found that overexpression of GspD (EpsD), the type II secretion system secretin, induces the Psp response, whereas otherV. choleraesecretins do not. In addition, we have identified several environmental conditions that induce this stress response. Our studies on the genetic regulation and induction of the Psp system inV. choleraesuggest that the key regulatory elements are conserved with those of other Gram-negative bacteria. While apspnull strain is fully capable of colonizing the infant mouse intestine, it exhibits a colonization defect in a zebrafish model, indicating that this response may be important for disease transmission in the environment. Overall, these studies provide an initial understanding of a stress response pathway that has not been previously investigated inV. cholerae.IMPORTANCEVibrio choleraeleads a dual life cycle, as it can exist in the aquatic environment and colonize the human small intestine. In both life cycles,V. choleraeencounters a variety of stressful conditions, including fluctuating pH and temperature and exposure to other agents that may negatively affect cell envelope homeostasis. The phage shock protein (Psp) response is required to sense and respond to such insults in other bacteria but has remained unstudied inV. cholerae. Interestingly, the Psp system has protein homologs, principally, PspA, in a number of bacterial clades as well as in archaea and plants. Therefore, our findings not only fill a gap in knowledge about an unstudied extracytoplasmic stress response inV. cholerae, but also may have far-reaching implications.

Summary A critical factor for bacterial survival in any environment is the ability to sense and respond appropriately to any stresses encountered. This is especially important for bacteria that inhabit environments that are constantly changing, or for those that inhabit more than one biological niche. Vibrio species are unique in that they are aquatic organisms, and must adapt to ever‐changing temperatures, salinity levels and nutrient concentrations. In addition, many species of Vibrio colonize other organisms, and must also deal with components of the host immune response. Vibrio infections of humans and other organisms have become more common in recent years, due to increasing water temperatures in many parts of the world. Therefore, understanding how these ubiquitous marine bacteria adapt to their changing environments is of importance. In this review, we discuss some of the ways that Vibrios sense and respond to the variety of stresses that negatively affect the bacterial cell envelope. Specifically, we will focus on what is currently known about the σE response, the Cpx response and the contributions of OmpU to extracytoplasmic stress relief.

Vibrio cholerae is a natural inhabitant of aquatic ecosystems worldwide, typically residing in coastal or brackish water. While more than 200 serogroups have been identified, only serogroups O1 and O139 have been associated with epidemic cholera. However, infections other than cholera can be caused by nonepidemic, non-O1/non-O139 V. cholerae strains, including gastroenteritis and extraintestinal infections. While V. cholerae can also survive in freshwater, that is typically only observed in regions of the world where cholera is endemic. We recently isolated V. cholerae from several locations in lakes and rivers in northwest Ohio. These isolates were all found to be non-O1/non-O139 V. cholerae strains, that would not cause cholera. However, these isolates contained a variety of virulence genes, including ctxA, rtxA, rtxC, hlyA, and ompU. Therefore, it is possible that some of these isolates have the potential to cause gastroenteritis or other infections in humans. We also investigated the relative motility of the isolates and their ability to form biofilms as this is important for V. cholerae survival in the environment. We identified one isolate that forms very robust biofilms, up to 4x that of our laboratory control strains. Finally, we investigated the susceptibility of these isolates to a panel of antibiotics. We found that many of the isolates showed decreased susceptibility to some of the antibiotics tested, which could be of concern. While we do not know if these isolates are pathogenic to humans, increased surveillance to better understand the public health risk to the local community should be considered.ImportanceThis study found that Vibrio cholerae belonging to non-O1/non-O139 serogroups is present in freshwater lakes and rivers in northwest Ohio. Although non-O1/non-O139 V. cholerae strains generally do not produce cholera toxin, and thus do not cause epidemic cholera, they often contain other virulence factors that may contribute to pathogenicity. In fact, we found that these local isolates contained an assortment of potential virulence genes. We also found that some of the isolates showed antibiotic resistance. While we do not currently know if the local V. cholerae strains are capable of causing disease in humans, increased monitoring for V. cholerae in the region is warranted in the interest of public health.

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