Iron uptake and metabolism by Salmonella enterica

Serovars of the genus Salmonella scavenge iron (III) chelated with low molecular weight compounds called siderophores. The transport of one such group of siderophores, the ferroxamines, was investigated using sensitivity growth stimulation bioassays. Uptake of all three ferrioxamines tested was demonstrated to be dependent upon transport across the outer membrane via the FoxA protein. Wild-type levels of transport required the TonB protein, however, lower yet significant transport of iron complexed with ferroixamines B and E, but not G, appeared to occur by a TonB-independent mechanism. Transport of all three ferrioxamines across the inner membrane, like all other hydroxamate siderophores, was found to be dependent on the periplasmic binding protein-dependent inner membrane ABC transporter consisting of FhuBCD. The distribution of the foxA receptor gene within the genus Salmonella was determined by DNA hybridisation and found to be limited to S. enterica subspecies, I, II and IIIb. S. enterica serovar Typhimurium strains unable to utilise ferrixoamines B, E and G as a sole of source of iron were found to have a small but significant disadvantage in colonising rabbit ileal loops compared to the wild-type parent strain. Furthermore, a strain containing this mutation was highly attenuated in mice after oral inoculation.;A range of structurally diverse -keto and -hydroxy acids promoted growth of a number of mutants of serovars of S. enterica subspecies I by a TonB-dependent mechanism. A S. enterica serovar Typhimurium strain containing a TnphoA insertion in the gene encoding the periplasmic binding protein component of an inner membrane ABC transporter system was found to be unable to utilise -keto acids at high iron limitation. Excretion of a number of -keto acids into culture supernatants occured in response to iron limitation and was found to be regulated by Fur.