Protection of Pseudomonas aeruginosa against ciprofloxacin and beta-lactams by homologous alginate

Abstract

Pseudomonas aeruginosa-derived alginate but no other neutral and negatively charged polysaccharides protected mucoid and nonmucoid strains of that organism against ciprofloxacin, gentamicin, ticarcillin, and ceftazidime. Data indicate that alginate has an intrinsic protective effect which is independent of diffusion, charge, or biofilm phenomena.The role of Pseudomonas aeruginosa in lung infections of patients with cystic fibrosis (CF) is well documented (1, 9, 12), but the means by which mucoid strains survive aggressive antibiotic therapy are ill defined. It has been suggested that the alginate may, among other things, directly protect the bacteria against antibiotics by facilitating a biofilm or microcolony mode of growth (7,8) Figure 1 shows the influence of P. aeruginosa alginate concentration on the survival of nonmucoid cells exposed to 0.1 jig of ciprofloxacin per ml. The protection afforded is clearly concentration dependent, with approximately 1, 2, 30, and 60% survivors after 15 min of exposure in the presence of 0, 0.125, 0.25, and 0.50% (wt/vol) alginate, respectively. Qualitatively similar but less-marked effects were observed when autologous alginate was added to washed cells of the mucoid strain (data not shown). The influences of various polymers on survival of the nonmucoid strain exposed to ciprofloxacin and gentamicin are shown in Fig. 2 and 3, respectively; again, qualitatively similar results were obtained with other strains. In each case, only alginate was protective, and that from P. aeruginosa was much more protective than that from seaweed. Controls (data not shown) demonstrated that none of the polymers influenced the growth or survival of any of the strains used, and the order of mixing of polymer, antibiotic, and inoculum had no influence on results. The protective effects of P. aeruginosa alginate on growing cultures of the nonmucoid strain ex-

Pseudomonas aeruginosa Biofilms Exposed to Imipenem Exhibit Changes in Global Gene Expression and β-Lactamase and Alginate Production

“…Increased production of alginate decreases the susceptibilities of bacteria growing in biofilms to numerous antibiotics. The penetration of antibiotics through the biofilm may be reduced due to binding to alginate, as has been reported for aminoglycosides, e.g., tobramycin (1,15,21,23). However, exposure to tobramycin does not affect the expression of alginate in P. aeruginosa biofilms (PAO1), as reported by Whiteley et al (50).…”

“…Chronic bronchopulmonary infection with P. aeruginosa is the major factor leading to the increased morbidity and premature mortality seen in patients with cystic fibrosis (CF) (26). The establishment of biofilms by alginate-producing P. aeruginosa strains is the most common mode of growth in CF patients with chronic lung infections, with the biofilms providing a protected environment against the host immune system and a number of antibiotics (1,4,15,23). The presence of P. aeruginosa strains with the mucoid phenotype in CF patients with chronic lung infections is a marker of a poor prognosis (20).…”

Interactions between Biocide Cationic Agents and Bacterial Biofilms

“…The negatively charged EPS produced by P. aeruginosa has been shown to bind to positively charged antibiotics such as aminoglycosides, but the resulting reduction in the diffusion coefficient within the biofilm has been shown to be insufficient to explain the observed changes in the susceptibility of the biofilm (29). The mucoid glycocalyx associated with the P. aeruginosa biofilm also protects the stuck cells against neutral antibiotics, indicating that factors other than charge are responsible for the reduced efficacies of antibiotics (22). Costerton (8) observed that ␤-lactam antibiotics can penetrate the entire thickness of the biofilm and so concluded that protection of biofilm cells is not really linked to slime.…”

Multidrug resistant pseudomonas aeruginosa in contemporary medical practice: findings from urinary isolates at a Nigerian university teaching hospital

“…aeruginosa possesses several virulence factors which aid in its pathogenicity and resistance to antimicrobial agents (Cane & Walsh, 1999;Lee, et al, 2003). These include: possession of mucus-an alginate capsule (Hodges, & Gordon, 1991;Owlia, et al, 2001;Ahangarzadeh-Rezaee, et al, 2002), presence of exoenzymes S, elastase and phospholipase C (Slack, & Nichols, 1981;Livermore, 1987;Behzadiyan-Nejad, et al, 1989); and an active Chaperone Usher pathway (Ichimiya, et al, 1994;Vallet, et al, 2001). P. aeruginosa has been shown to be resistant to several antibiotics.…”