The effect of iron on the toxigenicity of Vibrio cholerae.

Abstract

Abstract. In vitro and in vivo studies were conducted to assess the response of cholera toxin (CT) production to increasing iron concentrations in an aquatic environment. Production of CT by seven of eight Vibrio cholerae strains tested, including the Bengal strain (O139), was significantly enhanced in the presence of iron concentrations of 1.0 and 10 g/L. The exception (El Tor Ogawa) had a significant CT response only in the presence of 10 g of iron/L. Enhancement of CT production also occurred at iron concentrations less than 1.0 g/L, but not to a statistically significant degree. The high iron concentrations, which in this study were found to stimulate CT production, have been described by others in association with sediments, water plants, and chitinous fauna. Other investigators have shown a predilection by V. cholerae to attach to these sites in the aquatic environment. The importance of excess in vivo iron with respect to the pathogenicity of several gram-negative bacilli is well recognized. However, the possible impact of environmental iron on the in vitro toxigenicity of a microorganism, in this case V. cholerae in its aquatic environment, is to the best of our knowledge a new finding with important epidemiologic implications. These findings, coupled with the fact that iron concentration is considerably enhanced in industrially polluted waters and sediments, may reflect a causal link between the concurrent global upsurge of industrialization and pandemic occurrence of cholera during the latter half of the 20th century. Enhanced toxigenicity may also cause clinical disease following ingestion of lower than usual infective doses of cholera vibrios, thereby increasing the incidence of symptomatic cases and, possibly, of severe cases.Iron is an essential component of many enzymes and other proteins and is required for growth of virtually all bacteria. 1 The environment as well as animal hosts have limited amounts of free iron available for microbial growth since the metal forms insoluble complexes at neutral or alkaline pH and is sequestered in hosts by iron-binding proteins. One specific iron acquisition system found in some pathogens, including Vibrio cholerae, consists of a microbially produced iron-binding compound, or siderophore, and proteins associated with the transport and use of chelated iron. Environmental strains of V. cholerae produce more siderophore than clinical isolates. 2 The iron transport system is related to increased virulence of some invasive pathogens. Low or unavailable iron may trigger virulence factors such as the shiga toxin of Shigella dysenteriae, 3 diphtheria toxin of Corynebacterium diphtheriae, 4 shiga-like toxin I of enterohemorrhagic Escherichia coli, 5 and exotoxin A of Pseudomonas aeruginosa. 6,7 A previous study showed that V. cholerae survival time in water significantly increased with increasing iron levels up to optimum values of 0.1-1.0 g/L (pH 7) and 0.01-0.1 g/L (pH 9-11), above which survival decreased. 8 Vibrio cholerae is a noninvasive bacillus that exerts its ...

Stress and Stress-Induced Neuroendocrine Changes Increase the Susceptibility of Juvenile Oysters ( Crassostrea gigas ) to Vibrio splendidus

“…Iron is essential for the growth of several microbes (28), including the oyster parasite P. marinus (6), and for the pathogenicity of certain vibrios (21). Thus, the stressinduced secretion of NA may lead to a release of iron from oyster iron-chelating proteins and promote the replication and/or pathogenicity of V. splendidus in infected oysters.…”

Effects of Global Climate on Infectious Disease: the Cholera Model

“…Expression of CT is optimal at salinities between 2 and 2.5‰, independent of cell concentration (151). Furthermore, moderate levels of introduced iron also increase the expression of CT (125). Therefore, environmental triggers may become epidemiologically important for prevalence of the organism and its virulence (potentially resulting in shorter onset times and lower infectious doses).…”

Strain‐Specific Iron‐Dependent Virulence inEscherichia coli

“…In contrast, the blood and liver of mice injected with the nonvirulent strain contained relatively few bacteria. The numbers of nonvirulent E. coli present in the liver 4 h after ip injection with or without hemoglobin were for the entire liver and 6 1 ‫ע‬ 0.4 ϫ 10 3 ‫ע‬ ( ; ) for the virulent strains. 9 1.5 ϫ 10 n p 4 P p .002…”

“…Other explanations for this effect have included iron-dependent production of cytotoxins or leukotoxins by the virulent strains [5,6] and the preferential stimulation of growth of virulent strains due to the provision of iron, a nutrilite that is practically unavailable in normal mammalian body fluids [1,7,8]. In this regard, the action of siderophores that permit bacterial iron acquisition in low iron environments has been studied well and can be a virulence factor [9].…”