Synthesis of Lipoteichoic Acids in Bacillus anthracis

Abstract

bLipoteichoic acid (LTA), a glycerol phosphate polymer, is a component of the envelope of Gram-positive bacteria that has hitherto not been identified in Bacillus anthracis, the causative agent of anthrax. LTA synthesis in Staphylococcus aureus and other microbes is catalyzed by the product of the ltaS gene, a membrane protein that polymerizes polyglycerol phosphate from phosphatidyl glycerol. Here we identified four ltaS homologues, designated ltaS1 to -4, in the genome of Bacillus anthracis. Polyglycerol phosphate-specific monoclonal antibodies were used to detect LTA in the envelope of B. anthracis strain Sterne (pXO1؊ ) vegetative forms. B. anthracis mutants lacking ltaS1, ltaS2, ltaS3, or ltaS4 did not display defects in growth or LTA synthesis. In contrast, B. anthracis strains lacking both ltaS1 and ltaS2 were unable to synthesize LTA and exhibited reduced viability, altered envelope morphology, aberrant separation of vegetative forms, and decreased sporulation efficiency. Expression of ltaS1 or ltaS2 alone in B. anthracis as well as in other microbes was sufficient for polyglycerol phosphate synthesis. Thus, similar to S. aureus, B. anthracis employs LtaS enzymes to synthesize LTA, an envelope component that promotes bacterial growth and cell division.

Small molecule inhibitor of lipoteichoic acid synthesis is an antibiotic for Gram-positive bacteria

“…S1). Compound 1771-induced morphological changes resemble those observed for S. aureus and B. anthracis mutants with defects in LTA synthesis (14,18). For example, the chain length of the B. anthracis ltaS1/ltaS2 mutant is increased compared with WT ( Fig.…”

“…For example, the chain length of the B. anthracis ltaS1/ltaS2 mutant is increased compared with WT ( Fig. S1A), and its ability to form colonies is reduced by 1,000-fold (18).…”

“…Characterization of LtaS in Bacillus anthracis, Bacillus subtilis, and Listeria monocytogenes confirmed that membrane proteins with pfam00884 domains are indeed responsible for the synthesis of polyglycerol-phosphate LTA (7). Where examined, ltaS mutants exhibited diminished viability, increased cell size, and altered morphology (16)(17)(18)(19). These results suggested that LtaS of Gram-positive bacteria may represent an extracellular target for the development of antibiotics against drugresistant Gram-positive bacteria.…”

GacA is essential for Group A Streptococcus and defines a new class of monomeric dTDP‐4‐dehydrorhamnose reductases (RmlD)

“…Cultures were diluted in THY with or without theophylline to an OD 600 of 0.06 and grown to midlog phase. Samples were washed, fixed and dehydrated as described previously (Garufi et al ., 2012), mounted onto 12.5 mm specimen stubs (Agar scientific, Stansted, Essex, UK) and coated with gold to 1 nm using a Quorum Q150R S sputter coater at 20 mA. Visual examination was performed with a Phenom PRO desktop SEM (Phenom‐World BV).…”

Opening moves: early events in anthrax pathogenesis and their consequences for dissemination

“…The membrane of B. anthracis is relatively understudied compared to other parts of the surface, but is considered to have several similarities to the model organism B. subtilis [82]. The peptidoglycan layer was previously thought to lack lipoteichoic acid, but recent studies have determined the presence and gene products necessary for its formation [83]. In general, the peptidoglycan has a structure similar to the closely related B. cereus [82].…”