Genetic basis for sulfonamide resistance in Bacillus anthracis

Area of Science:

• Microbiology
• Biochemistry
• Drug Resistance

Background:

• Field strains of Bacillus anthracis show natural resistance to sulfonamide antimicrobials.
• Sulfonamides inhibit dihydropteroate synthase (DHPS), but the link to B. anthracis resistance is unclear.

Purpose of the Study:

• To investigate the connection between B. anthracis DHPS and sulfonamide resistance.
• To confirm if DHPS is responsible for the intrinsic sulfonamide resistance observed in B. anthracis.

Main Methods:

• Microdilution broth assays determined minimum inhibitory concentrations (MICs) for sulfonamides against B. anthracis Sterne.
• Polymerase chain reaction (PCR) amplified and cloned the putative DHPS gene (folP).
• Functional assays included complementation of an E. coli folP deletion mutant and enzyme activity tests.

Main Results:

• B. anthracis Sterne demonstrated high resistance to sulfonamides (MICs > 1250 microg/ml).
• The B. anthracis folP gene was successfully cloned, expressed, and confirmed to encode a functional DHPS.
• Transferring B. anthracis DHPS to an E. coli mutant conferred high-level sulfonamide resistance.

Conclusions:

• The study establishes a direct link between B. anthracis DHPS and sulfonamide resistance.
• Understanding this link is crucial for developing novel antimicrobials targeting DHPS for anthrax treatment.