The mono-ADP-ribosyltransferase (mART) toxins are contributing factors to a number of human diseases, including cholera, diphtheria, traveler's diarrhea, and whooping cough. VahC is a cytotoxic, actin-targeting mART from Aeromonas hydrophila PPD134/91. This bacterium is implicated primarily in diseases among freshwater fish species but also contributes to gastrointestinal and extraintestinal infections in humans. VahC was shown to ADP-ribosylate Arg-177 of actin, and the kinetic parameters were K(m)(NAD(+)) = 6 μM, K(m)(actin) = 24 μM, and k(cat) = 22 s(-1). VahC activity caused depolymerization of actin filaments, which induced caspase-mediated apoptosis in HeLa Tet-Off cells. Alanine-scanning mutagenesis of predicted catalytic residues showed the predicted loss of in vitro mART activity and cytotoxicity. Bioinformatic and kinetic analysis also identified three residues in the active site loop that were critical for the catalytic mechanism. A 1.9 Å crystal structure supported the proposed roles of these residues and their conserved nature among toxin homologues. Several small molecules were characterized as inhibitors of in vitro VahC mART activity and suramin was the best inhibitor (IC(50) = 20 μM). Inhibitor activity was also characterized against two other actin-targeting mART toxins. Notably, these inhibitors represent the first report of broad spectrum inhibition of actin-targeting mART toxins.

Traveler's diarrhea (TD) is a crucial area for research, as it affects millions of tourists each year and creates a large economic burden. More than 60% of TD cases are caused by a variety of bacterial enteropathogens: diarrhea-producing Escherichia coli, Shigella, Campylobacter, Salmonella, Aeromonas, Plesiomonas, and noncholera Vibrios. Noroviruses are also an important cause of morbidity among travelers. Recent studies have identified host genetic risk factors associated with susceptibility to pathogen-specific TD. Prevention strategies should be emphasized, as all individuals with TD experience approximately 24 hours of disability and 5-10% experience chronic functional bowel disease. Poorly absorbed rifaximin provides protection for trips lasting 2 weeks or less. TD vaccines are also currently in development. All individuals planning trips to developing regions should be armed with 1 of the 3 agents that have shown efficacy for self-treatment of TD: ciprofloxacin (or levofloxacin), rifaximin, or azithromycin, depending upon the location of the trip. Although global epidemiologic changes in etiologic agents as well as antibiotic resistance patterns have been better understood recently, changes should be expected during the next decade due to new prevention and treatment approaches.

Prulifloxacin, the prodrug of ulifloxacin (active component), is a newer fluoroquinolone with broad activity against enteric and nonenteric gram-negative bacilli. Ulifloxacin and other oral comparator agents were tested for activity against 582 gastroenteritis strains from global surveillance studies. Ulifloxacin was highly active against Escherichia coli, Salmonella spp., Shigella spp., Yersinia spp., Vibrio spp., Aeromonas spp., and Plesiomonas spp. (MIC(50)s and MIC(90)s, <or=0.03 microg/ml and <or=0.06 microg/ml, respectively). Only rare Aeromonas spp., Campylobacter spp., and E. coli displayed elevated MIC results (>or=4 microg/ml). Ciprofloxacin exhibited similar activity but was two- to fourfold less potent. Presently approved for clinical use in certain European countries and Japan, ulifloxacin was the most active of the antimicrobial agents tested against these gastroenteritis-causing pathogens.

Traveler's diarrhea (TD) is the most frequent health problem in travelers to developing countries. Several personal and environmental risk factors are at the basis of TD acquisition and are discussed in this paper. TD is caused by a wide range of infectious organisms, ETEC and EAEC bacteria strains being the main enteropathogens incriminated in TD. Other causative bacteria are: Shigella spp., Campylobacter spp., Vibrio spp., Aeromonas spp., Salmonella spp., and Plesiomonas spp. Parasite species are also included: Cyclospora cayetanensis, Giardia lamblia, Cryptosporidium, Entamoeba histolytica, as well as viruses: rotavirus, adenovirus, Norwalk virus. Due to the great diversity of pathogens incriminated, several pathophysiological mechanisms have been described and some of them are still poorly understood. The clinical symptoms present are also quite variable, although inflammatory and non-inflammatory diarrhea have been established as a classical and basic classification of diarrhea.

Traveler's diarrhea is the most common health problem of international travelers. We determined the prevalence of Aeromonas spp. associated with traveler's diarrhea and analyzed the geographic distribution, clinical features, and antimicrobial susceptibility. Aeromonas spp. were isolated as a cause of traveler's diarrhea in 18 (2%) of 863 patients. A. veronii biotype sobria was isolated in nine patients, A. caviae in seven patients, and A. jandaei and A. hydrophila in one patient each. Aeromonas spp. were isolated with a similar prevalence in Africa, Latin America, and Asia. Watery and persistent diarrhea, fever, and abdominal cramps were common complaints. All strains were resistant to ampicillin; showed variable resistance to chloramphenicol, tetracycline, and cotrimoxazole; and were susceptible to cefotaxime, ciprofloxacin, and nalidixic acid. The persistence of symptoms made antimicrobial treatment necessary.

Clinical efficacy of norfloxacin for treatment of traveler's diarrhea in 106 Finnish tourists vacationing in Morocco was evaluated during two different seasons. When the criteria for diagnosis of traveler's diarrhea were fulfilled, norfloxacin (400 mg) or a placebo was given orally, twice daily for 3 days. All symptoms and signs subsided sooner in the norfloxacin group. The clearest difference was observed in the duration of diarrhea: 1.2 days in the norfloxacin group vs. 3.3 days in the placebo group (P < .001). The duration of diarrhea due to particular species was as follows for the two groups: in cases due to Salmonella enterica, 1.1 vs 4.1 days (P < .01); in cases due to Campylobacter jejuni, 1.8 vs. 5.0 days (P < .01); and in cases due to enterotoxigenic Escherichia coli, 1.0 day vs. 3.1 days (P < .01). The rate of full recovery during administration of norfloxacin or a placebo was also greater among the norfloxacin recipients: 84% vs. 47% (P < .001). No significant adverse effects were reported. Norfloxacin proved to be safe and effective in therapy for traveler's diarrhea.