Endotoxins of Gram-negative microbes fulfill as components of the outer membrane a vital function for bacterial viability and, if set free, induce in mammalians potent pathophysiological effects. Chemically, they are lipopolysaccharides (LPS) consisting of an O-specific chain, a core oligosaccharide, and a lipid component, termed lipid A. The latter determines the endotoxic activities and, together with the core constituent Kdo, essential functions for bacteria. The primary structure of lipid A of various bacterial origin has been elucidated and lipid A of Escherichia coli has been chemically synthesized. The biological analysis of synthetic lipid A partial structures proved that the expression of endotoxic activity depends on a unique primary structure and a peculiar endotoxic conformation. The biological lipid A effects are mediated by macrophage-derived bioactive peptides such as tumor necrosis factor alpha (TNF). Macrophages possess LPS receptors, and the lipid A regions involved in specific binding a...

Bacterial endotoxin: molecular relationships of structure to activity and function.

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.

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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.

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.

This review is devoted to structural and serological characteristics of the O-antigens (O-polysaccharides) of the lipopolysaccharides of various Proteus species, which provide the basis for classifying Proteus strains to O-serogroups. The antigenic relationships of Proteus strains within and beyond the genus as well as their O-antigen-related bioactivities are also discussed.

https://journals.sagepub.com/doi/pdf/10.1177/1753425909360668

Structure and serology of O-antigens as the basis for classification of Proteus strains

Murine monoclonal and rabbit polyclonal antibodies raised against the lipopolysaccharides (LPS) of Re mutants of Salmonella minnesota, Proteus mirabilis, and Escherichia coli were serologically characterized. Using natural Re LPS and natural and synthetic partial structures thereof, representing the 3-deoxy-D-manno-2-octulosonic acid (KDO) or lipid A region or both, the epitope specificities of four monoclonal antibodies were defined. Clones 20 (immunoglobulin M [IgM]) and 25 (IgG3) recognize a terminal alpha-pyranosidically linked KDO monosaccharide residue and the alpha-2,4-linked KDO disaccharide, respectively, as the immunodominant group. Therefore, these two antibodies are core antibodies which do not require the presence of lipid A constituents for binding. The minimal structure enabling binding of clone 17 (IgG2b) is a pseudotetrasaccharide of the sequence alpha-KDO-(2----4)-alpha-KDO-(2----6)-beta-glucosamine-(1----6)- glucosaminitol with two amide-linked 3-hydroxytetradecanoic acid residues. The smallest structure with which clone 22 (IgG3) reacted was de-O-acylated Re LPS. Therefore, clones 17 and 22 are LPS antibodies requiring both the lipid A and the KDO region for binding. Phosphoryl residues of the lipid A moiety in Re LPS are dispensable for the reaction with clone 17, whereas they are necessary for that with clone 22. These four different antibody types were also detected in polyclonal rabbit antisera and could be distinguished from each other by absorption experiments. It was found that type 20 and 25 antibodies either were not present or were present only in small amounts and that the majority of the antibodies were of types 17 and 22. From these data, we conclude that the immunodominant structures of Re LPS comprise both the KDO and lipid A domains.

Epitope specificities of murine monoclonal and rabbit polyclonal antibodies against enterobacterial lipopolysaccharides of the Re chemotype.

The genus Proteus belongs to the Enterobacteriaceae family, where it is placed in the tribe Proteeae, together with the genera Morganella and Providencia. Currently, the genus Proteus consists of five species: P. mirabilis, P. vulgaris, P. penneri, P. hauseri and P. myxofaciens, as well as three unnamed Proteus genomospecies. The most defining characteristic of Proteus bacteria is a swarming phenomenon, a multicellular differentiation process of short rods to elongated swarmer cells. It allows population of bacteria to migrate on solid surface. Proteus bacteria inhabit the environment and are also present in the intestines of humans and animals. These microorganisms under favorable conditions cause a number of infections including urinary tract infections (UTIs), wound infections, meningitis in neonates or infants and rheumatoid arthritis. Therefore, Proteus is known as a bacterial opportunistic pathogen. It causes complicated UTIs with a higher frequency, compared to other uropathogens. Proteus infections are accompanied by a formation of urinary stones, containing struvite and carbonate apatite. The virulence of Proteus rods has been related to several factors including fimbriae, flagella, enzymes (urease - hydrolyzing urea to CO2 and NH3, proteases degrading antibodies, tissue matrix proteins and proteins of the complement system), iron acqusition systems and toxins: hemolysins, Proteus toxin agglutinin (Pta), as well as an endotoxin - lipopolysaccharide (LPS). Proteus rods form biofilm, particularly on the surface of urinary catheters, which can lead to serious consequences for patients. In this review we present factors involved in the regulation of swarming phenomenon, discuss the role of particular pathogenic features of Proteus spp., and characterize biofilm formation by these bacteria.

https://www.degruyter.com/downloadpdf/j/fobio.2012.8.issue-1/fobio-2013-0001/fobio-2013-0001.xml

Proteus sp. – an opportunistic bacterial pathogen – classification, swarming growth, clinical significance and virulence factors

Determination of the epitope specificity of monoclonal antibodies against the inner core region of bacterial lipopolysaccharides by use of 3-deoxy-D-manno-octulosonate-containing synthetic antigens.

Antoni Rozalski

Papers

Potential virulence factors of Proteus bacilli.

Structure and serology of O-antigens as the basis for classification of Proteus strains

Epitope specificities of murine monoclonal and rabbit polyclonal antibodies against enterobacterial lipopolysaccharides of the Re chemotype.

Proteus sp. – an opportunistic bacterial pathogen – classification, swarming growth, clinical significance and virulence factors

Determination of the epitope specificity of monoclonal antibodies against the inner core region of bacterial lipopolysaccharides by use of 3-deoxy-D-manno-octulosonate-containing synthetic antigens.