scholarly journals A Pathway Closely Related to the d-Tagatose Pathway of Gram-Negative Enterobacteria Identified in the Gram-Positive Bacterium Bacillus licheniformis

2013 ◽  
Vol 79 (11) ◽  
pp. 3511-3515 ◽  
Author(s):  
Edwige Van der Heiden ◽  
Michaël Delmarcelle ◽  
Sarah Lebrun ◽  
Régine Freichels ◽  
Alain Brans ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Gene Cluster ◽  
Bacillus Licheniformis ◽  
Klebsiella Oxytoca ◽  
Negative Bacterium ◽  
Positive Bacterium ◽  
Gram Positive ◽  
Gram Negative ◽  
Content Type ◽  
Bacterium Bacillus

ABSTRACTWe report the first identification of a gene cluster involved ind-tagatose catabolism inBacillus licheniformis. The pathway is closely related to thed-tagatose pathway of the Gram-negative bacteriumKlebsiella oxytoca, in contrast to thed-tagatose 6-phosphate pathway described in the Gram-positive bacteriumStaphylococcus aureus.

scholarly journals Antimicrobial Activity of Omadacycline Tested against Clinical Bacterial Isolates from Hospitals in Mainland China, Hong Kong, and Taiwan: Results from the SENTRY Antimicrobial Surveillance Program (2013 to 2016)

2019 ◽  
Vol 63 (3) ◽  
Author(s):  
Cecilia G. Carvalhaes ◽  
Michael D. Huband ◽  
Harald H. Reinhart ◽  
Robert K. Flamm ◽  
Helio S. Sader
Keyword(s):  
Staphylococcus Aureus ◽  
Hong Kong ◽  
Klebsiella Oxytoca ◽  
Surveillance Program ◽  
Gram Positive ◽  
Gram Negative ◽  
Content Type ◽  
Vancomycin Resistant ◽  
Geographic Regions

ABSTRACTOmadacycline is a derivative of minocycline and the first agent of the aminomethylcycline class. A total of 3,282 organisms (1 per patient) were consecutively collected from patients hospitalized in China (including Hong Kong) and Taiwan. Susceptibility testing was performed by broth microdilution methods in a central laboratory (JMI Laboratories). The collection included Gram-positive and Gram-negative organisms from patients with pneumonia, bloodstream, skin, community-acquired respiratory, and other infections. Omadacycline was very potent againstStaphylococcus aureus(n= 689; MIC50/90, 0.12/0.25 mg/liter), including methicillin-resistantStaphylococcus aureus(MRSA;n= 299; MIC50/90, 0.12/0.5 mg/liter), and had similar activity across geographic regions. Omadacycline was very active againstStreptococcus pneumoniae(highest MIC, 0.25 mg/liter), β-hemolytic streptococci (highest MIC, 1 mg/liter), viridans group streptococci (highest MIC, 0.25 mg/liter), andEnterococcusspp. (highest MIC, 0.5 mg/liter) from all geographic regions. Overall, 53.8% ofS. pneumoniaeisolates were penicillin resistant (penicillin MIC, ≥2 mg/liter) and 10.7% of enterococci (21.2% amongE. faeciumisolates) were vancomycin resistant. Omadacycline was active againstHaemophilus influenzae(MIC50/90, 0.5/1 mg/liter) regardless of β-lactamase production and was active againstMoraxella catarrhalis(MIC50/90, ≤0.12/0.25 mg/liter). AgainstEnterobacteriaceae, omadacycline was most active againstEscherichia coli(MIC50/90, 1/2 mg/liter),Klebsiella oxytoca(MIC50/90, 1/4 mg/liter), andEnterobacter cloacae(MIC50/90, 2/4 mg/liter). Omadacycline had potentin vitroactivity against Gram-positive and Gram-negative pathogens isolated from China and Taiwan and retained activity against problem pathogens, such as MRSA, vancomycin-resistant enterococci (VRE), penicillin-resistantS. pneumoniae(PRSPN), and extended-spectrum β-lactamase-producingE. coli. The observed MIC profile in Chinese isolates was very similar to that seen in the U.S. and European surveillance studies.

scholarly journals Nitroxide Functionalized Antibiotics Are Promising Eradication Agents against Staphylococcus aureus Biofilms

2019 ◽  
Vol 64 (1) ◽  
Author(s):  
Anthony D. Verderosa ◽  
Rabeb Dhouib ◽  
Kathryn E. Fairfull-Smith ◽  
Makrina Totsika
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Biofilms ◽  
Gram Positive ◽  
Gram Negative ◽  
Content Type ◽  
Microscopy Analysis ◽  
Biofilm Dispersal ◽  
Biofilm Structure ◽  
Dispersal Activity

ABSTRACT Treatment of biofilm-related Staphylococcus aureus infections represents an important medical challenge worldwide, as biofilms, even those involving drug-susceptible S. aureus strains, are highly refractory to conventional antibiotic therapy. Nitroxides were recently shown to induce the dispersal of Gram-negative biofilms in vitro, but their action against Gram-positive bacterial biofilms remains unknown. Here, we demonstrate that the biofilm dispersal activity of nitroxides extends to S. aureus, a clinically important Gram-positive pathogen. Coadministration of the nitroxide CTEMPO (4-carboxy-2,2,6,6-tetramethylpiperidin-1-yloxyl) with ciprofloxacin significantly improved the biofilm eradication activity of the antibiotic against S. aureus. Moreover, covalently linking the nitroxide to the antibiotic moiety further reduced the ciprofloxacin minimal biofilm eradication concentration. Microscopy analysis revealed that fluorescent nitroxide-antibiotic hybrids could penetrate S. aureus biofilms and enter cells localized at the surface and base of the biofilm structure. No toxicity to human cells was observed for the nitroxide CTEMPO or the nitroxide-antibiotic hybrids. Taken together, our results show that nitroxides can mediate the dispersal of Gram-positive biofilms and that dual-acting biofilm eradication antibiotics may provide broad-spectrum therapies for the treatment of biofilm-related infections.

scholarly journals Surveillance of Omadacycline Activity against Clinical Isolates from a Global Collection (North America, Europe, Latin America, Asia-Western Pacific), 2010-2011

2017 ◽  
Vol 61 (5) ◽  
Author(s):  
Michael A. Pfaller ◽  
Michael D. Huband ◽  
Paul R. Rhomberg ◽  
Robert K. Flamm
Keyword(s):  
Latin America ◽  
North America ◽  
Klebsiella Oxytoca ◽  
Enterobacter Aerogenes ◽  
Community Acquired Pneumonia ◽  
Asia Pacific ◽  
Gram Positive ◽  
Gram Negative ◽  
Content Type ◽  
Viridans Group Streptococci

ABSTRACT Omadacycline is a broad-spectrum aminomethylcycline in late-stage clinical development for the treatment of acute bacterial skin and skin structure infections and community-acquired pneumonia as an oral and an intravenous once-daily formulation. In this study, omadacycline and comparators were tested against 69,246 nonduplicate bacterial isolates collected prospectively during 2010 and 2011 from medical centers in Asia-Pacific (11,397 isolates), Europe (23,490 isolates), Latin America (8,038 isolates), and North America (26,321 isolates). Omadacycline was tested by broth microdilution following Clinical and Laboratory Standards Institute M07-A10 (2015) methods. A total of 99.9% of Staphylococcus aureus isolates were inhibited by ≤2 μg/ml of omadacycline (MIC50/90, 0.12/0.25 μg/ml), including 100.0% of methicillin-susceptible S. aureus isolates and 99.8% of methicillin-resistant S. aureus isolates. Omadacycline potencies were comparable for Streptococcus pneumoniae (MIC50/90, 0.06/0.06 μg/ml), viridans group streptococci (MIC50/90, 0.06/0.12 μg/ml), and beta-hemolytic streptococci (MIC50/90, 0.06/0.12 μg/ml) regardless of species and susceptibility to penicillin. Omadacycline was active against Enterobacteriaceae and was most active against Escherichia coli (MIC50/90, 0.5/2 μg/ml), Enterobacter aerogenes (MIC50/90, 2/4 μg/ml), Klebsiella oxytoca (MIC50/90, 1/4 μg/ml), and Citrobacter spp. (MIC50/90, 1/4 μg/ml). Omadacycline was active against Haemophilus influenzae (MIC50/90, 1/1 μg/ml) regardless of β-lactamase status and against Moraxella catarrhalis (MIC50/90, 0.12/0.25 μg/ml). The potent activity of omadacycline against Gram-positive and Gram-negative bacteria indicates that omadacycline merits further study in serious infections in which multidrug resistance and mixed Gram-positive and Gram-negative infections may be a concern.

scholarly journals Draft Genome Sequence of the Thermophilic Bacterium Bacillus licheniformis SMIA-2, an Antimicrobial- and Thermostable Enzyme-Producing Isolate from Brazilian Soil

2020 ◽  
Vol 9 (17) ◽  
Author(s):  
Samara Pinto Custodio Bernardo ◽  
Albert Remus R. Rosana ◽  
Adriane Nunes de Souza ◽  
Sorina Chiorean ◽  
Meire Lelis Leal Martins ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Genome Sequence ◽  
Bacillus Licheniformis ◽  
Draft Genome ◽  
Thermophilic Bacterium ◽  
Thermostable Enzyme ◽  
Draft Genome Sequence ◽  
Antimicrobial Compound ◽  
Content Type ◽  
Bacterium Bacillus

Bacillus licheniformis SMIA-2, a thermophilic and thermostable enzyme-producing bacterium, is found to be active against several strains of Staphylococcus aureus and several Bacillus species. Here, we report the 4.30-Mbp draft genome and bioinformatic predictions supporting gene inventories for amylase, protease, cellulase, xylanase, and antimicrobial compound biosynthesis.

scholarly journals The ω Subunit Governs RNA Polymerase Stability and Transcriptional Specificity in Staphylococcus aureus

2016 ◽  
Vol 199 (2) ◽  
Author(s):  
Andy Weiss ◽  
Brittney D. Moore ◽  
Miguel H. J. Tremblay ◽  
Dale Chaput ◽  
Astrid Kremer ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Rna Polymerase ◽  
Gram Negative Bacteria ◽  
Sequencing Analysis ◽  
Gram Positive ◽  
Gram Negative ◽  
Content Type ◽  
Successful Infection ◽  
Transcriptional Changes ◽  
First Time

ABSTRACT Staphylococcus aureus is a major human pathogen that causes infection in a wide variety of sites within the human body. Its ability to adapt to the human host and to produce a successful infection requires precise orchestration of gene expression. While DNA-dependent RNA polymerase (RNAP) is generally well characterized, the roles of several small accessory subunits within the complex have yet to be fully explored. This is particularly true for the omega (ω or RpoZ) subunit, which has been extensively studied in Gram-negative bacteria but largely neglected in Gram-positive counterparts. In Escherichia coli, it has been shown that ppGpp binding, and thus control of the stringent response, is facilitated by ω. Interestingly, key residues that facilitate ppGpp binding by ω are not conserved in S. aureus, and consequently, survival under starvation conditions is unaffected by rpoZ deletion. Further to this, ω-lacking strains of S. aureus display structural changes in the RNAP complex, which result from increased degradation and misfolding of the β′ subunit, alterations in δ and σ factor abundance, and a general dissociation of RNAP in the absence of ω. Through RNA sequencing analysis we detected a variety of transcriptional changes in the rpoZ-deficient strain, presumably as a response to the negative effects of ω depletion on the transcription machinery. These transcriptional changes translated to an impaired ability of the rpoZ mutant to resist stress and to fully form a biofilm. Collectively, our data underline, for the first time, the importance of ω for RNAP stability, function, and cellular physiology in S. aureus. IMPORTANCE In order for bacteria to adjust to changing environments, such as within the host, the transcriptional process must be tightly controlled. Transcription is carried out by DNA-dependent RNA polymerase (RNAP). In addition to its major subunits (α2ββ′) a fifth, smaller subunit, ω, is present in all forms of life. Although this small subunit is well studied in eukaryotes and Gram-negative bacteria, only limited information is available for Gram-positive and pathogenic species. In this study, we investigated the structural and functional importance of ω, revealing key roles in subunit folding/stability, complex assembly, and maintenance of transcriptional integrity. Collectively, our data underline, for the first time, the importance of ω for RNAP function and cellular harmony in S. aureus.

scholarly journals Identification of a d-Arabinose-5-Phosphate Isomerase in the Gram-Positive Clostridium tetani

2017 ◽  
Vol 199 (17) ◽  
Author(s):  
David L. Cech ◽  
Katherine Markin ◽  
Ronald W. Woodard
Keyword(s):  
Sequence Similarity ◽  
Physiological Role ◽  
Gram Negative Bacteria ◽  
Positive Bacterium ◽  
Gram Positive ◽  
Clostridium Tetani ◽  
High Sequence Similarity ◽  
Gram Negative ◽  
Content Type ◽  
Sugar Phosphates

ABSTRACT d-Arabinose-5-phosphate (A5P) isomerases (APIs) catalyze the interconversion of d-ribulose-5-phosphate and d-arabinose-5-phosphate. Various Gram-negative bacteria, such as the uropathogenic Escherichia coli strain CFT073, contain multiple API paralogs (KdsD, GutQ, KpsF, and c3406) that have been assigned various cellular functions. The d-arabinose-5-phosphate formed by these enzymes seems to play important roles in the biosynthesis of lipopolysaccharide (LPS) and group 2 K-antigen capsules, as well as in the regulation of the cellular d-glucitol uptake and uropathogenic infectivity/virulence. The genome of a Gram-positive pathogenic bacterium, Clostridium tetani, contains a gene encoding a putative API, C. tetani API (CtAPI), even though C. tetani lacks both LPS and capsid biosynthetic genes. To better understand the physiological role of d-arabinose-5-phosphate in this Gram-positive organism, recombinant CtAPI was purified and characterized. CtAPI displays biochemical characteristics similar to those of APIs from Gram-negative organisms and complements the API deficiency of an E. coli API knockout strain. Thus, CtAPI represents the first d-arabinose-5-phosphate isomerase to be identified and characterized from a Gram-positive bacterium. IMPORTANCE The genome of Clostridium tetani, a pathogenic Gram-positive bacterium and the causative agent of tetanus, contains a gene (the CtAPI gene) that shares high sequence similarity with those of genes encoding d-arabinose-5-phosphate isomerases. APIs play an important role within Gram-negative bacteria in d-arabinose-5-phosphate production for lipopolysaccharide biosynthesis, capsule formation, and regulation of cellular d-glucitol uptake. The significance of our research is in identifying and characterizing CtAPI, the first Gram-positive API. Our findings show that CtAPI is specific to the interconversion of arabinose-5-phosphate and ribulose-5-phosphate while having no activity with the other sugars and sugar phosphates tested. We have speculated a regulatory role for this API in C. tetani, an organism that does not produce lipopolysaccharide.

scholarly journals Efficacy of Ceftaroline Fosamil against Penicillin-Sensitive and -Resistant Streptococcus pneumoniae in an Experimental Rabbit Meningitis Model

2013 ◽  
Vol 57 (10) ◽  
pp. 4653-4655 ◽  
Author(s):  
P. Cottagnoud ◽  
M. Cottagnoud ◽  
F. Acosta ◽  
A. Stucki
Keyword(s):  
Staphylococcus Aureus ◽  
Streptococcus Pneumoniae ◽  
Bactericidal Activity ◽  
Resistant Strain ◽  
Gram Positive ◽  
Ceftaroline Fosamil ◽  
Gram Negative ◽  
Methicillin Resistant ◽  
Content Type ◽  
Gram Negative Organisms

ABSTRACTCeftaroline is a new cephalosporin with bactericidal activity against resistant Gram-positive organisms, including methicillin-resistantStaphylococcus aureus(MRSA) and penicillin-resistantStreptococcus pneumoniae, as well as common Gram-negative organisms. This study tested the prodrug, ceftaroline fosamil, against a penicillin-sensitive and a penicillin-resistant strain ofS. pneumoniaein an experimental rabbit meningitis model. The penetration of ceftaroline into inflamed meninges was approximately 14%. Ceftaroline fosamil was slightly superior to ceftriaxone against the penicillin-sensitive strain and significantly superior to the combination of ceftriaxone and vancomycin against the penicillin-resistant strain.

scholarly journals ComparativeIn VitroActivities of SMT19969, a New Antimicrobial Agent, against Clostridium difficile and 350 Gram-Positive and Gram-Negative Aerobic and Anaerobic Intestinal Flora Isolates

2013 ◽  
Vol 57 (10) ◽  
pp. 4872-4876 ◽  
Author(s):  
Ellie J. C. Goldstein ◽  
Diane M. Citron ◽  
Kerin L. Tyrrell ◽  
C. Vreni Merriam
Keyword(s):  
Staphylococcus Aureus ◽  
Clostridium Difficile ◽  
Intestinal Flora ◽  
Colonization Resistance ◽  
Gram Positive ◽  
Gram Negative ◽  
Content Type ◽  
Aerobic And Anaerobic ◽  
Group Species

ABSTRACTThe comparativein vitroactivity of SMT19969, a novel, narrow-spectrum, nonabsorbable agent, was studied against 50 ribotype-definedClostridium difficilestrains, 174 Gram-positive and 136 Gram-negative intestinal anaerobes, and 40 Gram-positive aerobes. SMT19969 was one dilution more active againstC. difficileisolates (MIC range, 0.125 to 0.5 μg/ml; MIC90, 0.25 μg/ml), including ribotype 027 strains, than fidaxomicin (range, 0.06 to 1 μg/ml; MIC90, 0.5 μg/ml) and two to six dilutions lower than either vancomycin or metronidazole. SMT19969 and fidaxomicin were generally less active against Gram-negative anaerobes, especially theBacteroides fragilisgroup species, than vancomycin and metronidazole, suggesting that SMT19969 has a lesser impact on the normal intestinal microbiota that maintain colonization resistance. SMT19969 showed limited activity against other Gram-positive anaerobes, includingBifidobacteriaspecies,Eggerthella lenta,Finegoldia magna, andPeptostreptococcus anaerobius, with MIC90s of >512, >512, 64, and 64 μg/ml, respectively.Clostridiumspecies showed various levels of susceptibility, withC. innocuumbeing susceptible (MIC90, 1 μg/ml) andC. ramosumandC. perfringensbeing nonsusceptible (MIC90, >512 μg/ml). Activity againstLactobacillusspp. (range, 0.06 to >512 μg/ml; MIC90, >512 μg/ml) was comparable to that of fidaxomicin and varied by species and strain. Gram-positive aerobic cocci (Staphylococcus aureus,Enterococcus faecalis,E. faecium, and streptococci) showed high SMT19969 MIC90values (128 to >512 μg/ml).

scholarly journals In Vitro Activity of Ceftaroline against Gram-Positive and Gram-Negative Pathogens Isolated from Patients in Canadian Hospitals in 2009

2011 ◽  
Vol 55 (6) ◽  
pp. 2837-2846 ◽  
Author(s):  
James A. Karlowsky ◽  
Heather J. Adam ◽  
Melanie R. DeCorby ◽  
Philippe R. S. Lagacé-Wiens ◽  
Daryl J. Hoban ◽  
...  
Keyword(s):  
Staphylococcus Epidermidis ◽  
Klebsiella Oxytoca ◽  
Canadian Hospital ◽  
Gram Positive ◽  
Gram Negative ◽  
Content Type ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Recent Collection

ABSTRACTThein vitroactivities of ceftaroline and comparative agents were determined for a collection of the most frequently isolated bacterial pathogens from hospital-associated patients across Canada in 2009 as part of the ongoing CANWARD surveillance study. In total, 4,546 isolates from 15 sentinel Canadian hospital laboratories were tested using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method. Compared with other cephalosporins, including ceftobiprole, cefepime, and ceftriaxone, ceftaroline exhibited the greatest potency against methicillin-susceptibleStaphylococcus aureus(MSSA), with a MIC90of 0.25 μg/ml. Ceftaroline also demonstrated greater potency than ceftobiprole against community-associated methicillin-resistantS. aureus(MRSA) (MIC90, 0.5 μg/ml) and health care-associated MRSA (MIC90, 1 μg/ml) and was at least 4-fold more active than other cephalosporins againstStaphylococcus epidermidis; all isolates of MSSA and MRSA tested were susceptible to ceftaroline (MIC, ≤1 μg/ml). Against streptococci, includingStreptococcus pneumoniae, ceftaroline MICs (MIC90, ≤0.03 μg/ml) were comparable to those of ceftobiprole; however, against penicillin-nonsusceptible, macrolide-nonsusceptible, and multidrug-nonsusceptible isolates ofS. pneumoniae, ceftaroline demonstrated 2- to 4-fold and 4- to 16-fold more potent activities than those of ceftobiprole and ceftriaxone, respectively. All isolates ofS. pneumoniaetested were susceptible to ceftaroline (MIC, ≤0.25 μg/ml). Among Gram-negative isolates, ceftaroline demonstrated potent activity (MIC90, ≤0.5 μg/ml) againstEscherichia coli(92.2% of isolates were susceptible),Klebsiella pneumoniae(94.1% of isolates were susceptible),Proteus mirabilis(97.7% of isolates were susceptible), andHaemophilus influenzae(100% of isolates were susceptible). Ceftaroline demonstrated less potent activity (MIC90, ≥4 μg/ml) againstEnterobacterspp.,Acinetobacter baumannii,Pseudomonas aeruginosa,Klebsiella oxytoca,Serratia marcescens, andStenotrophomonas maltophilia. Overall, ceftaroline demonstrated potentin vitroactivity against a recent collection of the most frequently encountered Gram-positive and Gram-negative isolates from patients attending hospitals across Canada in 2009.

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