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Journal ArticleDOI

Potential virulence factors of Proteus bacilli.

01 Mar 1997-Microbiology and Molecular Biology Reviews (American Society for Microbiology)-Vol. 61, Iss: 1, pp 65-89
TL;DR: The genus Proteus, which contains bacteria considered now to belong to the opportunistic pathogens, has its most characteristic attribute, swarming growth, enabling them to colonize and survive in higher organisms.
Abstract: 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.
Citations
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Journal ArticleDOI
TL;DR: Current knowledge concerning the different strategies bacteria employ to resist the activities of polymyxins are summarized and 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.
Abstract: 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.

988 citations


Cites background from "Potential virulence factors of Prot..."

  • ...…Proteus spp., Providencia spp., Morganella morganii (all three collectively referred to as the Proteeae tribe), Serratia spp., Edwardsiella tarda and Burkholderia cepacia complex (Muyembe et al., 1973; Rozalski et al., 1997; Loutet and Valvano, 2011; Biswas et al., 2012; Samonis et al., 2014)....

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  • ...…Pseudomonas aeruginosa and Burkholderia cepacia complex Vaara et al., 1981; Boll et al., 1994; Nummila et al., 1995; Helander et al., 1996; Rozalski et al., 1997; Trent et al., 2001b; Moskowitz et al., 2004; Yan et al., 2007; Loutet and Valvano, 2011; Lin et al., 2014 Modification of the…...

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Journal ArticleDOI
TL;DR: 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.
Abstract: 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.

735 citations


Cites background from "Potential virulence factors of Prot..."

  • ...mirabilis strains are still pathogenic in the urinary tract (201, 213, 331)....

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  • ...Proteus CPSs tend to be acidic due to the presence of uronic acid, pyruvate, or phosphate groups, thus enabling this structure to bind to metal cations such as Ca(2) and Mg(2) (331)....

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  • ...Proteus CPSs tend to be acidic due to the presence of uronic acid, pyruvate, or phosphate groups, thus enabling this structure to bind to metal cations such as Ca2 and Mg2 (331)....

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  • ...In most Proteus strains, the general structure of the O-specific polysaccharides has been found to be acidic due to the presence of uronic acids and various noncarbohydrate acidic components, including phosphate groups (187, 331)....

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  • ...It is produced during swarmer cell differentiation and is stimulated by divalent cations (Ca2 Mg2 ) (433)....

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Journal ArticleDOI
TL;DR: Bacterial lipopolysaccharides are the major components of the outer surface of Gram-negative bacteria and are often of interest in medicine for their immunomodulatory properties.

497 citations

Journal ArticleDOI
TL;DR: 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.
Abstract: 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.

408 citations

References
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Journal ArticleDOI
TL;DR: It is becoming increasingly clear that the outer membrane is very important in the physiology of gram-negative bacteria in making them resistant to host defense factors such as lysozyme, P-lysin, and various leukocyte proteins.

2,357 citations


"Potential virulence factors of Prot..." refers background in this paper

  • ...In particular, OmpA is effective as an immunomodulator of the immune response to LPS, greatly enhancing the level of O-specific IgG (125, 127, 199)....

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Journal ArticleDOI
TL;DR: Chelators (such as EDTA, nitrilotriacetic acid, and sodium hexametaphosphate), which disintegrate the outer membrane by removing Mg2+ and Ca2+, are effective and valuable permeabilizers.

1,718 citations


"Potential virulence factors of Prot..." refers background in this paper

  • ...This results in a disorganization of the outer and inner membranes of gram-negative bacteria (290, 292)....

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Journal ArticleDOI
TL;DR: 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, and molecular and submolecular details of the specificity of the interaction of lipid A with responsive host cells are determined.
Abstract: 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...

1,573 citations


"Potential virulence factors of Prot..." refers background in this paper

  • ...Biologically, LPS are endotoxins, well-known pathogenic factors of gram-negative bacteria, which cause a broad spectrum of pathophysiological effects such as fever, hypotension, disseminated intravascular coagulation, and lethal shock (231)....

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Journal ArticleDOI
TL;DR: This review summarizes the virtual explosion of information regarding the epidemiology, biochemistry, mechanisms of action, and genetic basis of these urovirulence factors that has occurred in the past decade and identifies areas in need of further study.
Abstract: Uropathogenic strains of Escherichia coli are characterized by the expression of distinctive bacterial properties, products, or structures referred to as virulence factors because they help the organism overcome host defenses and colonize or invade the urinary tract. Virulence factors of recognized importance in the pathogenesis of urinary tract infection (UTI) include adhesins (P fimbriae, certain other mannose-resistant adhesins, and type 1 fimbriae), the aerobactin system, hemolysin, K capsule, and resistance to serum killing. This review summarizes the virtual explosion of information regarding the epidemiology, biochemistry, mechanisms of action, and genetic basis of these urovirulence factors that has occurred in the past decade and identifies areas in need of further study. Virulence factor expression is more common among certain genetically related groups of E. coli which constitute virulent clones within the larger E. coli population. In general, the more virulence factors a strain expresses, the more severe an infection it is able to cause. Certain virulence factors specifically favor the development of pyelonephritis, others favor cystitis, and others favor asymptomatic bacteriuria. The currently defined virulence factors clearly contribute to the virulence of wild-type strains but are usually insufficient in themselves to transform an avirulent organism into a pathogen, demonstrating that other as-yet-undefined virulence properties await discovery. Virulence factor testing is a useful epidemiological and research tool but as yet has no defined clinical role. Immunological and biochemical anti-virulence factor interventions are effective in animal models of UTI and hold promise for the prevention of UTI in humans. Images

1,290 citations


"Potential virulence factors of Prot..." refers background in this paper

  • ...Common bacterial properties involved in the infection process include adhesion to epithelial surfaces, invasion (penetration) of host cells, intracellular multiplication of the pathogen, colonization of the cell tissue or transmission to a new susceptible host, production of enzymes which damage the host defense system, and synthesis of toxins (91, 110)....

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Journal ArticleDOI
TL;DR: The crystal structure of the K. aerogenes enzyme has been determined and provides important insight into the mechanism of catalysis, and accessory genes have been shown to be required for activation of urease apoprotein, and roles for the accessory proteins in metallocenter assembly have been proposed.

1,244 citations