Interference of the CadC regulator in the arginine-dependent acid resistance system of Shigella and enteroinvasive E. coli.
A typical pathoadaptive mutation of Shigella and enteroinvasive Escherichia coli (EIEC) is the inactivation of the cad locus which comprises the genes necessary for lysine decarboxylation, an enzyme involved in pH homoeostasis. In E. coli, the cadBA operon, encoding lysine decarboxylase (CadA) and a lysine cadaverine antiporter (CadB), is submitted to the control of CadC, a positive activator whose gene maps upstream the operon, and is transcribed independently from the same strand. CadC is an integral inner membrane protein which acts both, as signal sensor and as transcriptional regulator responding to the low pH and lysine signals. Analysis of the molecular rearrangements responsible for the loss of lysine decarboxylase activity in Shigella and EIEC has revealed that the inactivation of the cadC gene is a common feature. The 3 major adaptive acid resistance (AR) systems - AR1, AR2, and AR3 - are known to be activated at low pH by Shigella and E. coli, allowing them to withstand extremely acid conditions. In this study, evaluating the survival of S. flexneri, S. sonnei, and EIEC strains complemented with a functional cadC gene and challenged at low pH, we present evidence that CadC negatively regulates the expression of the arginine-dependent adaptive acid-resistance system (AR3), encoded by the adi locus while it has no effect on the expression of AR1 and AR2 systems. Moreover, since our results indicate that in enteroinvasive strains the presence of CadC reduces the expression of the arginine decarboxylase encoding gene adiA, it is possible to hypothesize that the loss of functionality of lysine decarboxylase is counterbalanced by a higher expression of the adi system, and that CadC, besides specifically affecting the regulation of the cadBA operon, is also relevant to other systems responding to low pH.
Casalino
Mariassunta
M
Dipartimento di Biologia, Università Roma Tre, 00146 Rome, Italy.
Prosseda
Gianni
G
Barbagallo
Marialuisa
M
Iacobino
Angelo
A
Ceccarini
Paolo
P
Latella
Maria Carmela
MC
Nicoletti
Mauro
M
Colonna
Bianca
B
D000143:Acids / Q000633:toxicity*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D002262:Carboxy-Lyases / Q000096:biosynthesis; D015169:Colony Count, Microbial; D015536:Down-Regulation; D004926:Escherichia coli / Q000235:genetics / Q000502:physiology*; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D017930:Genes, Reporter; D005816:Genetic Complementation Test; D050296:Microbial Viability / Q000187:drug effects; D008954:Models, Biological; D008969:Molecular Sequence Data; D012760:Shigella / Q000235:genetics / Q000502:physiology*; D013312:Stress, Physiological; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D000143:Acids; D001426:Bacterial Proteins; C080050:CadC protein, Bacteria; D001616:beta-Galactosidase; D002262:Carboxy-Lyases; C019722:arginine decarboxylase