Polymyxins are polycationic antimicrobial peptides that are currently the last-resort antibiotics for the treatment of multidrug-resistant, Gram-negative bacterial infections. The reintroduction of polymyxins for antimicrobial therapy has been followed by an increase in reports of resistance among Gram-negative bacteria. Some bacteria, such as Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii, develop resistance to polymyxins in a process referred to as acquired resistance, whereas other bacteria, such as Proteus spp., Serratia spp. and Burkholderia spp., are naturally resistant to these drugs. Reports of polymyxin resistance in clinical isolates have recently increased, including acquired and intrinsically resistant pathogens. This increase is considered a serious issue, prompting concern due to the low number of currently available effective antibiotics. This review summarizes current knowledge concerning the different strategies bacteria employ to resist the activities of polymyxins. Gram-negative bacteria employ several strategies to protect themselves from polymyxin antibiotics (polymyxin B and colistin), including a variety of lipopolysaccharide (LPS) modifications, such as modifications of lipid A with phosphoethanolamine and 4-amino-4-deoxy-L-arabinose, in addition to the use of efflux pumps, the formation of capsules and overexpression of the outer membrane protein OprH, which are all effectively regulated at the molecular level. The increased understanding of these mechanisms is extremely vital and timely to facilitate studies of antimicrobial peptides and find new potential drugs targeting clinically relevant Gram-negative bacteria.

/pdf/mechanisms-of-polymyxin-resistance-acquired-and-intrinsic-3p0boc30m7.pdf

Mechanisms of polymyxin resistance: acquired and intrinsic resistance in bacteria

Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia: The 'red complex', a prototype polybacterial pathogenic consortium in periodontitis

Catheter-associated urinary tract infections (CAUTIs) represent the most common type of nosocomial infection and are a major health concern due to the complications and frequent recurrence. These infections are often caused by Escherichia coli and Proteus mirabilis. Gram-negative bacterial species that cause CAUTIs express a number of virulence factors associated with adhesion, motility, biofilm formation, immunoavoidance, and nutrient acquisition as well as factors that cause damage to the host. These infections can be reduced by limiting catheter usage and ensuring that health care professionals correctly use closed-system Foley catheters. A number of novel approaches such as condom and suprapubic catheters, intermittent catheterization, new surfaces, catheters with antimicrobial agents, and probiotics have thus far met with limited success. While the diagnosis of symptomatic versus asymptomatic CAUTIs may be a contentious issue, it is generally agreed that once a catheterized patient is believed to have a symptomatic urinary tract infection, the catheter is removed if possible due to the high rate of relapse. Research focusing on the pathogenesis of CAUTIs will lead to a better understanding of the disease process and will subsequently lead to the development of new diagnosis, prevention, and treatment options.

/pdf/complicated-catheter-associated-urinary-tract-infections-due-4k0xw7kb6h.pdf

Complicated Catheter-Associated Urinary Tract Infections Due to Escherichia coli and Proteus mirabilis

Structure of bacterial lipopolysaccharides.

Summary Effectors of the innate immune system, the antibacterial peptides, have pivotal roles in preventing infection at epithelial surfaces. Here we show that proteinases of the significant human pathogens Pseudomonas aeruginosa , Enterococcus faecalis , Proteus mirabilis and Streptococcus pyogenes, degrade the antibacterial peptide LL-37. Analysis by mass spectrometry of fragments generated by P. aeruginosa elastase in vitro revealed that the initial cleavages occurred at Asn-Leu and Asp-Phe, followed by two breaks at Arg-Ile, thus inactivating the peptide. Proteinases of the other pathogens also degraded LL37 as determined by SDS-PAGE. Ex vivo , P. aeruginosa elastase induced LL-37 degradation in human wound fluid, leading to enhanced bacterial survival. The degradation was blocked by the metalloproteinase inhibitors GM6001 and 1, 10-phenantroline (both of which inhibited P. aeruginosa elastase, P. mirabilis proteinase, and E. faecalis gelatinase), or the inhibitor E64 (which inhibited S. pyogenes cysteine proteinase). Additional experiments demonstrated that dermatan sulphate and disaccharides of the structure [D UA(2S)-GalNAc(4,6S)], or sucroseoctasulphate, inhibited the degradation of LL-37. The results indicate that proteolytic degradation of LL-37 is a common virulence mechanism and that molecules which block this degradation could have therapeutic potential.

/pdf/proteinases-of-common-pathogenic-bacteria-degrade-and-47k9n8z3q8.pdf

Proteinases of common pathogenic bacteria degrade and inactivate the antibacterial peptide LL-37

The object of this review is the genus Proteus, which contains bacteria considered now to belong to the opportunistic pathogens. Widely distributed in nature (in soil, water, and sewage), Proteus species play a significant ecological role. When present in the niches of higher macroorganisms, these species are able to evoke pathological events in different regions of the human body. The invaders (Proteus mirabilis, P. vulgaris, and P. penneri) have numerous factors including fimbriae, flagella, outer membrane proteins, lipopolysaccharide, capsule antigen, urease, immunoglobulin A proteases, hemolysins, amino acid deaminases, and, finally, the most characteristic attribute of Proteus, swarming growth, enabling them to colonize and survive in higher organisms. All these features and factors are described and commented on in detail. The questions important for future investigation of these facultatively pathogenic microorganisms are also discussed.

Potential virulence factors of Proteus bacilli.

The chemical composition and serological activity of free lipid A from Proteus were studied. Only two fatty acids: myristic acid and 3-hydroxymyristic acid were detected. When calculated for glucosamine disaccharide unit, 2 moles of ester-linked and 1 mole of amide-linked fatty acid are present. Amino group of glucosaminyl residue is substituted by 3-hydroxymyristic acid. The occurence of an uncommon (4-aminoarabinose) substituent, attached outside the backbone, was noticed. The results of serological investigation indicate the great similarity between antigenic determinants of Proteus lipid A and Salmonella-type of lipid.

Immunochemical studies on free lipid A from Proteus mirabilis 1959.

Terminal non-reducing position of GalUA residue in the R core region of P. mirabilis R110 (Ra)mutant was established by GLC/MS analysis of methylated degraded polysaccharide. This position of GalUA is exceptional as compared with the terminal constituents present in the known structures of R core polysaccharides in Enterobacteriaceae. As it was shown in serological study, GalUA does not play a role of immunodominant in the examined Proteus R core region.

Kotełko K

Papers

Potential virulence factors of Proteus bacilli.

Immunochemical studies on free lipid A from Proteus mirabilis 1959.

Galacturonic acid as the terminal constituent in the R core polysaccharide of proteus R110 (Ra) mutant.

Badanie wybranych wlasciwosci biologicznych komorek dlugich [swarm cells] Proteus mirabilis