Ross Cana L, Thomason Kerrie S, Koehler Theresa M
Department of Microbiology and Molecular Genetics, University of Texas-Houston Medical School, Houston, Texas 77030, USA.
J Bacteriol. 2009 Nov;191(21):6683-93. doi: 10.1128/JB.00691-09. Epub 2009 Aug 28.
The susceptibility of most Bacillus anthracis strains to beta-lactam antibiotics is intriguing considering that the closely related species Bacillus cereus and Bacillus thuringiensis typically produce beta-lactamases and the B. anthracis genome harbors two beta-lactamase genes, bla1 and bla2. We show that beta-lactamase activity associated with B. anthracis is affected by two genes, sigP (BA2502) and rsiP (BA2503), predicted to encode an extracytoplasmic function sigma factor and an anti-sigma factor, respectively. Deletion of the sigP-rsiP locus abolished beta-lactamase activity in a naturally occurring penicillin-resistant strain and had no effect on beta-lactamase activity in a prototypical penicillin-susceptible strain. Complementation with sigP and rsiP from the penicillin-resistant strain, but not with sigP and rsiP from the penicillin-susceptible strain, conferred constitutive beta-lactamase activity in both mutants. These results are attributed to a nucleotide deletion near the 5' end of rsiP in the penicillin-resistant strain that is predicted to result in a nonfunctional protein. B. cereus and B. thuringiensis sigP and rsiP homologues are required for inducible penicillin resistance in these species. Expression of the B. cereus or B. thuringiensis sigP and rsiP genes in a B. anthracis sigP-rsiP-null mutant confers inducible production of beta-lactamase activity, suggesting that while B. anthracis contains the genes necessary for sensing beta-lactam antibiotics, the B. anthracis sigP and rsiP gene products are not sufficient for bla induction.
考虑到密切相关的蜡状芽孢杆菌和苏云金芽孢杆菌通常会产生β-内酰胺酶，而炭疽芽孢杆菌基因组中含有两个β-内酰胺酶基因bla1和bla2，大多数炭疽芽孢杆菌菌株对β-内酰胺类抗生素敏感这一现象令人着迷。我们发现，与炭疽芽孢杆菌相关的β-内酰胺酶活性受两个基因sigP（BA2502）和rsiP（BA2503）影响，预计这两个基因分别编码一种胞外功能σ因子和一种抗σ因子。sigP - rsiP基因座的缺失消除了天然青霉素抗性菌株中的β-内酰胺酶活性，而对典型的青霉素敏感菌株中的β-内酰胺酶活性没有影响。用青霉素抗性菌株的sigP和rsiP进行互补，但不用青霉素敏感菌株的sigP和rsiP进行互补，能使两个突变体都产生组成型β-内酰胺酶活性。这些结果归因于青霉素抗性菌株中rsiP 5'端附近的一个核苷酸缺失，预计这会导致产生无功能的蛋白质。蜡状芽孢杆菌和苏云金芽孢杆菌的sigP和rsiP同源物是这些物种中诱导性青霉素抗性所必需的。在炭疽芽孢杆菌sigP - rsiP缺失突变体中表达蜡状芽孢杆菌或苏云金芽孢杆菌的sigP和rsiP基因可诱导产生β-内酰胺酶活性，这表明虽然炭疽芽孢杆菌含有感知β-内酰胺类抗生素所需的基因，但炭疽芽孢杆菌的sigP和rsiP基因产物不足以诱导bla。
