Moraxella catarrhalis: Clinical significance, antimicrobial susceptibility and BRO beta-lactamases

McGregor, Karen F.; Chang, Barbara J.; Mee, Brian; Riley, Thomas V.

doi:10.1007/bf01699978

Cited by 49 publications

(9 citation statements)

References 213 publications

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“…Its activity on clinical isolates of M. catarrhalis [19] is interesting, as such a bacterium is considered to be the third commonest pathogen of the respiratory tract in humans after Streptococcus pneumoniae and Haemophilus influenzae, responsible for otitis media in children and lower respiratory tract infections in the elderly [34]. In addition, the widespread production of b-lactamase renders M. catarrhalis resistant to penicillins [35], as also observed in GE23077-sensitive M. catarrhalis strains (E. Selva, unpublished data).…”

Section: Discussionmentioning

confidence: 99%

Mode of action of the microbial metabolite GE23077, a novel potent and selective inhibitor of bacterial RNA polymerase

Sarubbi

Monti

Corti

et al. 2004

European Journal of Biochemistry

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GE23077, a novel microbial metabolite recently isolated from Actinomadura sp. culture media, is a potent and selective inhibitor of bacterial RNA polymerase (RNAP). It inhibits Gram-positive (Bacillus subtilis) and Gram-negative (Escherichia coli) RNAPs with IC 50 values (i.e. the concentration at which the enzyme activity is inhibited by 50%) in the 10 )8 M range, whereas it is not active on E. coli DNA polymerase or on eukaryotic (wheat germ) RNAP II (IC 50 values > 10 )4 M in both cases). In spite of its potent activity on purified bacterial RNAPs, GE23077 shows a narrow spectrum of antimicrobial activity on Gram-positive and Gram-negative bacteria. To investigate the molecular basis of this behaviour, the effects of GE23077 on macromolecular biosynthesis were tested in E. coli cells permeabilized under different conditions. The addition of GE23077 to plasmolyzed cells resulted in an immediate and specific inhibition of intracellular RNA biosynthesis, in a dose-response manner, strongly suggesting that cell penetration is the main obstacle for effective antimicrobial activity of the antibiotic. Biochemical studies were also conducted with purified enzymes to obtain further insights into the mode of action of GE23077. Interestingly, the compound displays a behaviour similar to that of rifampicin, an antibiotic structurally unrelated to GE23077: both compounds act at the level of transcription initiation, but not on the r subunit and not on the formation of the promoter DNA-RNAP complex. Tests on different rifampicin-resistant E. coli RNAPs did not show any cross-resistance between the two compounds, indicating distinct binding sites on the target enzyme. In conclusion, GE23077 is an interesting new molecule for future mechanistic studies on bacterial RNAP and for its potential in anti-infective drug discovery.Keywords: antibiotic; cell permeabilization; natural product; rifampicin; transcription initiation. DNA-directed RNA polymerase (EC 2.7.7.6; RNAP) is the central enzyme of bacterial gene expression, responsible for all cellular RNA synthesis [1]. The catalytically competent ÔcoreÕ RNAP consists of five subunits (a 2 bb¢x, with a combined molecular mass of % 400 kDa) and is capable of elongation and termination. The initiation-competent ÔholoÕ RNAP is composed of the core enzyme and of an additional subunit, r, which confers on RNAP the ability to initiate transcription at specific promoter sites [2,3]. After over four decades of intensive research, RNAP is currently the subject of renewed interest and excitement, owing to recent publication of the crystal structures of the core [4] and holo [5,6] enzymes, and of an RNAP-DNA complex [7].The transcription process consists of three main stages: initiation, elongation and termination. Transcription initiation is a multistep process [8] in which holo RNAP specifically binds to promoter DNA at positions )35 and )10 to form an RNAP-promoter closed complex, melts the DNA duplex around the )10 region to yield an RNAPpromoter open complex, and then initiates transc...

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Section: Discussionmentioning

confidence: 99%

Mode of action of the microbial metabolite GE23077, a novel potent and selective inhibitor of bacterial RNA polymerase

Sarubbi

Monti

Corti

et al. 2004

European Journal of Biochemistry

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“…Underlying cardiopulmonary disease, chronic obstructive lung disease and cigarette smoking are common predisposing factors. M. Catarrhalis has also been reported to cause bacteremia, endocarditis, meningitis and keratitis in patients with cancer, neutropenia and respiratory tract diseases [6,7]. …”

Section: Discussionmentioning

confidence: 99%

Moraxella Catarrhalis peritonitis

2012

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SummaryBackground:Peritonitis continues to be a major complication of peritonitis in peritoneal dialysis patients. Recent advances in connectology and better patient training have decreased the incidence of peritonitis in the last two decades. Peritonitis in PD patients is usually due to gram positive and less often due to gram negative organisms. Herein we report a case of peritonitis due to Moraxella Catarrhalis and review the literature on the diagnosis and treatment of this rare cause of peritonitis.Case Report:Our patient was a 56 year old man with end stage renal disease, on peritoneal dialysis, who was totally asymptomatic and on routine clinic visit was noted to have a high white blood cell count in his peritoneal fluid. Due to the nature of the organism, it took two weeks and two different microbiology laboratories to identify the organism and provide proper treatment.Conclusions:Peritonitis is the major cause of peritoneal dialysis failure and prompt recognition of the causative agent is of crucial importance to the proper and timely management of this complication.

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“…Invasive infection due to M. catarrhalis may occur in immunocompromised individuals but is uncommon [5, 6, 8, 11, 18]. M. catarrhalis can lead to community acquired as well as nosocomial infections [9, 13, 16, 19]. M. catarrhalis can be isolated from blood, nasopharyngeal secretions, sputum, tracheal secretions, bronchoalveolar lavage, wound swabs, and tissue cultures e.g.…”

Section: Discussionmentioning

confidence: 99%

“…Consequently when M. catarrhalis is considered to be the causative organism, the choice of an empiric antimicrobial therapy should be a beta-lactamase resistant antibiotic [23]. The strains of M. catarrhalis are resistant to benzylpenicillin, ampicillin, amoxicillin and lincomycin and are usually susceptible to certain cephalosporins, macrolides, tetracyclines, and fluoroquinolones in addition to the combination of trimethoprim-sulfamethoxazole [8–10, 15, 19, 24]. Ceftriaxone has highly favorable pharmacokinetics which allow once daily dosing regimens to be employed even in the most severe infections associated with cancer therapy [25].…”

Section: Discussionmentioning

confidence: 99%

Pneumonia Caused by Moraxella Catarrhalis in Haematopoietic Stem Cell Transplant

Ka¹,

Fa²,

Na³

et al. 2007

Libyan J Med

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Moraxella catarrhalis is a gram negative diplococcus that causes a variety of upper and lower respiratory tract infections. Patients with malignant, hematological disorders treated with intensive cytotoxic chemotherapy, and recipients of various forms of haematopoietic stem cell transplant receiving immunosuppressive agents are at high risk of developing severe infections and septic complications. Early detection of the organism and prompt treatment with appropriate antibiotics provide both resolution of the infection and prevention of further consequences. Two patients with haematopoietic stem cell transplant who developed pneumonia caused by M. catarrhalis at King Faisal Specialist Hospital and Research Centre in Riyadh are reported and the literature is reviewed. To our knowledge, these are the first case reports of M. catarrhalis pneumonia in haematopoietic stem cell transplant patients.

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Moraxella catarrhalis: Clinical significance, antimicrobial susceptibility and BRO beta-lactamases

Cited by 49 publications

References 213 publications

Mode of action of the microbial metabolite GE23077, a novel potent and selective inhibitor of bacterial RNA polymerase

Mode of action of the microbial metabolite GE23077, a novel potent and selective inhibitor of bacterial RNA polymerase

Moraxella Catarrhalis peritonitis

Pneumonia Caused by Moraxella Catarrhalis in Haematopoietic Stem Cell Transplant

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