Pelvic Inflammatory Disease: A Review with Emphasis on Antimicrobial Therapy

Burnakis, Thomas G.; Hildebrandt, Nancy B.

doi:10.1093/clinids/8.1.86

Cited by 48 publications

(31 citation statements)

References 207 publications

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“…Gonococci grown anaerobically in media containing CMP-Neu5Ac become serum resistant two to three times faster than aerobic gonococci and incorporated almost six times as much sialic acid into their LOS, attributable to 4-fold increased STase activity as well as increased expression of sialylatable LNnT LOS (Frangipane and Rest 1993). These findings are relevant to humans, where gonococci encounter anaerobic conditions (Chow, Patten and Marshall 1979;Burnakis and Hildebrandt 1986), in part because of competition between neutrophils and bacteria for oxygen (Britigan and Cohen 1986).…”

Section: Gonococcal Sialyltransferase (Stase)mentioning

confidence: 98%

Gonococcal lipooligosaccharide sialylation: virulence factor and target for novel immunotherapeutics

Ram

Shaughnessy

Oliveira

et al. 2017

Pathogens and Disease

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One sentence summary: Lipooligosaccharide sialic acid, a key virulence factor for gonococci, can be targeted by novel immunotherapeutics to overcome multidrug-resistant gonorrhea. Editor: Alison Criss ABSTRACTGonorrhea has become resistant to most conventional antimicrobials used in clinical practice. The global spread of multidrug-resistant isolates of Neisseria gonorrhoeae could lead to an era of untreatable gonorrhea. New therapeutic modalities with novel mechanisms of action that do not lend themselves to the development of resistance are urgently needed. Gonococcal lipooligosaccharide (LOS) sialylation is critical for complement resistance and for establishing infection in humans and experimental mouse models. Here we describe two immunotherapeutic approaches that target LOS sialic acid: (i) a fusion protein that comprises the region in the complement inhibitor factor H (FH) that binds to sialylated gonococci and IgG Fc (FH/Fc fusion protein) and (ii) analogs of sialic acid that are incorporated into LOS but fail to protect the bacterium against killing. Both molecules showed efficacy in the mouse vaginal colonization model of gonorrhea and may represent promising immunotherapeutic approaches to target multidrug-resistant isolates. Disabling key gonococcal virulence mechanisms is an effective therapeutic strategy because the reduction of virulence is likely to be accompanied by a loss of fitness, rapid elimination by host immunity and consequently, decreased transmission.

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Section: Gonococcal Sialyltransferase (Stase)mentioning

confidence: 98%

Gonococcal lipooligosaccharide sialylation: virulence factor and target for novel immunotherapeutics

Ram

Shaughnessy

Oliveira

et al. 2017

Pathogens and Disease

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“…Treatment failure has been noticed in as many as 33% of patients [43] and increased frequency of abscess formation has been observed [44]. A recent review stated that therapy with penicillin either alone or with an aminoglycoside or tetracycline failed in 15-25% of cases [45]. This increased failure rate may be due to the increased resistance to penicillin among Bacteroides spp.…”

Section: Beta-lactamase In Clinical Infectionsmentioning

confidence: 99%

“…Early treatment of PID has been shown to reduce the effects of the infection on the fallopian tubes [45] and decreases the incidence of serious sequelae. Antimicro bial therapy should be aimed at the eradication of both aerobic and anaerobic bacterial pathogens as well as C. trachomatis.…”

Section: Therapeutic Implications Of Indirect Pathogenicity On the Mamentioning

confidence: 99%

The Role of Beta-Lactamase-Producing Bacteria in Obstetrical and Gynecological Infections

Brook

1991

Gynecol Obstet Invest

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Pelvic inflammatory disease (PID) is a polymicrobial infection that evolves multiple aerobic and anaerobic bacteria. Several of the bacterial pathogens that participate in PID can produce the enzyme beta lactamase. These include Bacteroides species (including Bacteroides bivius, Bacteroides disiens, and Bacteroides fragilis group), Neisseria gonorrheae,Enterobacteriaceae and Staphylococcus aureus. A recent increase in numbers of beta-lacta-mase-producing strains of these organisms in PID has been associated with increased failure rates of penicillins in eradication of this infection. These organisms cannot only survive penicillin therapy but also protect penicillin-susceptible pathogens from the drug. These direct and indirect virulence characteristics of beta-lactamase-producing bacteria require the administration of appropriate antimicrobial therapy directed against all of these pathogens in the therapy of PID.

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“…2,1989 infection are the cervix, rectum, pharynx, and genitourinary tract. In addition, gonococcal pelvic inflammatory disease is often a mixed infection with obligate anaerobes (6). Kellogg et al (29) reported the growth of N. gonorrhoeae under low oxygen tension and its survival under anaerobic conditions.…”

Section: Sulfur Metabolismmentioning

confidence: 99%

Physiology and metabolism of Neisseria gonorrhoeae and Neisseria meningitidis: implications for pathogenesis

et al. 1989

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Gonococci and meningococci are obligate human pathogens that can infect diverse sites within the human host. Each of these sites represents a unique niche with respect to nutrients, environmental factors, and competing microorganisms. The growth environment has a marked effect on the metabolism and cellular composition of Neisseria gonorrhoeae and N. meningitidis. Altered cellular composition is often reflected by changes in the cell surface that can ultimately affect the interaction of these microorganisms with the human host. The physiology and metabolism of the pathogenic Neisseria spp. have not been reviewed since 1979 (41). This review will discuss selected areas that have implications for the pathogenesis of these important microorganisms. IRON METABOLISMAfter entry into the human host, N. gonorrhoeae and N. meningitidis must multiply to colonize mucosal surfaces and to establish an infection. Cell growth and multiplication require essential nutrients such as iron. To obtain iron, the pathogenic Neisseria spp. must acquire it from the host. Despite the relative abundance of iron in the host, there is little free iron because of its sequestration by the ironbinding proteins transferrin (TF) and lactoferrin (LF) (19). In serum and interstitial fluid, iron is associated with TF; in breast milk, semen, and mucosal surfaces, it is associated primarily with LF. Consequently, gonococci and meningococci must possess mechanisms for utilizing the iron associated with the host iron-binding proteins as well as other potential in vivo iron sources such as heme and hemoglobin.Several studies have implicated iron in the virulence of the pathogenic Neisseria spp. Calver et al. (7) demonstrated that injection of ferrous sulfate prior to or injection of either iron sorbitol citrate or iron-dextran concomitantly with injection of N. meningitidis increased the lethality of several different meningococcal serogroups for mice by up to a 106-fold. The effect of the added iron was partially abrogated by the prior incubation of N. meningitidis with Desferal (CIBA-GEIGY Corp.), an iron chelator from which meningococci and gonococci are unable to remove iron (36). Holbein et al. (24) showed that the 50% lethal dose of N. meningitidis strains in a mouse model was decreased 109-fold by the concomitant administration of iron-dextran with the inoculum. Payne and Finkelstein (50) found that the intravenous inoculation of iron-containing compounds together with avirulent (nonpiliated) gonococci increased the lethality of these avirulent organisms for chicken embryos.Hafiz et al. (20) All strains of N. gonorrhoeae and N. meningitidis are able to grow with 25% iron-saturated TF as their sole source of iron (37). Archibald and DeVoe (1, 2) found that meningococci were capable of obtaining iron from a variety of iron-containing compounds including gastric mucin, ferric citrate, hemoglobin, myoglobin, and human TF. Iron complexed with a number of metabolic organic acids, polyphosphates, and several synthetic polycarboxylic acids was also re...

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Pelvic Inflammatory Disease: A Review with Emphasis on Antimicrobial Therapy

Cited by 48 publications

References 207 publications

Gonococcal lipooligosaccharide sialylation: virulence factor and target for novel immunotherapeutics

Gonococcal lipooligosaccharide sialylation: virulence factor and target for novel immunotherapeutics

The Role of Beta-Lactamase-Producing Bacteria in Obstetrical and Gynecological Infections

Physiology and metabolism of Neisseria gonorrhoeae and Neisseria meningitidis: implications for pathogenesis

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