Role of Phosphoglucomutase of Stenotrophomonas maltophilia in Lipopolysaccharide Biosynthesis, Virulence, and Antibiotic Resistance (original) (raw)

2003, Infection and Immunity

A homologue of the algC gene, responsible for the production of a phosphoglucomutase (PGM) associated with LPS and alginate biosynthesis in Pseudomonas aeruginosa, spgM, was cloned from Stenotrophomonas maltophilia. The spgM gene was shown to encode a bifunctional enzyme with both PGM and phosphomannomutase activities. Mutants lacking spgM produced less LPS than the SpgM ؉ parent strain and had a tendency for shorter O polysaccharide chains. No changes in LPS chemistry were obvious as a result of the loss of spgM. Significantly, however, spgM mutants displayed a modest increase in susceptibility to several antimicrobial agents and were completely avirulent in an animal model of infection. The latter finding may relate to the resultant serum sensitivity of spgM mutants which, unlike the wild-type parent strain, were rapidly killed by human serum. These data highlight the contribution made by LPS to the antimicrobial resistance and virulence of S. maltophilia. Stenotrophomonas maltophilia is a gram-negative bacterium that is an important cause of nosocomial infections (17, 34). It has emerged as an important opportunistic pathogen in immunodeficient patients, including transplant recipients (38), cancer patients (33), and AIDS sufferers (19). However, the most frequent site of infection remains the lungs (4, 9, 20). In many cases, treatment of S. maltophilia is problematic owing to its high level of intrinsic resistance to multiple classes of antibiotics (56). A number of factors, including multidrug efflux pumps (1, 3, 65) and outer membrane impermeability (13, 37), likely contribute to the intrinsic antibiotic resistance of S. maltophilia. A key component of the outer membrane is lipopolysaccharide (LPS), and changes in LPS structure have been correlated with changes in resistance to a variety of antimicrobial agents (reviewed in reference 41). Several groups have investigated LPS in S. maltophilia in an effort to assess its contribution to antimicrobial resistance in this organism (43-45, 60). S. maltophilia exhibits a temperature-dependent variation in susceptibility to several antibiotics, including aminoglycosides and polymyxin B (60), whose activities are known to be affected by LPS (44), but not quinolones, ␤-lactams, and chloramphenicol (44, 60). Temperature-dependent changes in outer membrane fluidity (44), LPS side-chain length (45) and, possibly, core phosphate content (43) appear to explain the temperature-dependent variation in aminoglycoside susceptibility, implicating LPS as a determinant of aminoglycoside resistance in this organism. Temperaturedependent changes in lipid A (44), outer membrane proteins (45), or 3-deoxy-D-manno-octulosonic acid (43) have not been observed.