scholarly journals Dissemination and Characteristics of a Novel Plasmid-Encoded Carbapenem-Hydrolyzing Class D β-Lactamase, OXA-436, Found in Isolates from Four Patients at Six Different Hospitals in Denmark

2017 ◽  
Vol 62 (1) ◽  
Author(s):  
Ørjan Samuelsen ◽  
Frank Hansen ◽  
Bettina Aasnæs ◽  
Henrik Hasman ◽  
Bjarte Aarmo Lund ◽  
...  
Keyword(s):  
Amino Acid ◽  
Sequence Type ◽  
Amino Acid Sequences ◽  
Citrobacter Freundii ◽  
Activity Profile ◽  
Content Type ◽  
Class D ◽  
Chromosomal Genes ◽  
Enterobacter Asburiae

ABSTRACT The diversity of OXA-48-like carbapenemases is continually expanding. In this study, we describe the dissemination and characteristics of a novel carbapenem-hydrolyzing class D β-lactamase (CHDL) named OXA-436. In total, six OXA-436-producing Enterobacteriaceae isolates, including Enterobacter asburiae (n = 3), Citrobacter freundii (n = 2), and Klebsiella pneumoniae (n = 1), were identified in four patients in the period between September 2013 and April 2015. All three species of OXA-436-producing Enterobacteriaceae were found in one patient. The amino acid sequence of OXA-436 showed 90.4 to 92.8% identity to the amino acid sequences of other acquired OXA-48-like variants. Expression of OXA-436 in Escherichia coli and kinetic analysis of purified OXA-436 revealed an activity profile similar to that of OXA-48 and OXA-181, with activity against penicillins, including temocillin; limited or no activity against extended-spectrum cephalosporins; and activity against carbapenems. The bla OXA-436 gene was located on a conjugative ∼314-kb IncHI2/IncHI2A plasmid belonging to plasmid multilocus sequence typing sequence type 1 in a region surrounded by chromosomal genes previously identified to be adjacent to bla OXA genes in Shewanella spp. In conclusion, OXA-436 is a novel CHDL with functional properties similar to those of OXA-48-like CHDLs. The described geographical spread among different Enterobacteriaceae and the plasmid location of bla OXA-436 illustrate its potential for further dissemination.

scholarly journals OXA-235, a Novel Class D β-Lactamase Involved in Resistance to Carbapenems in Acinetobacter baumannii

2013 ◽  
Vol 57 (5) ◽  
pp. 2121-2126 ◽  
Author(s):  
Paul G. Higgins ◽  
Francisco J. Pérez-Llarena ◽  
Esther Zander ◽  
Ana Fernández ◽  
Germán Bou ◽  
...  
Keyword(s):  
Amino Acid ◽  
Acinetobacter Baumannii ◽  
Carbapenem Resistance ◽  
The United States ◽  
Amino Acid Sequences ◽  
Insertion Sequences ◽  
Content Type ◽  
Resistance Determinants ◽  
Class D ◽  
Amino Acid Variants

ABSTRACTWe investigated the mechanism of carbapenem resistance in 10Acinetobacter baumanniistrains isolated from the United States and Mexico between 2005 and 2009. The detection of known metallo-β-lactamase or carbapenem-hydrolyzing oxacillinase (OXA) genes by PCR was negative. The presence of plasmid-encoded carbapenem resistance genes was investigated by transformation ofA. baumanniiATCC 17978. Shotgun cloning experiments and sequencing were performed, followed by the expression of a novel β-lactamase inA. baumannii. Three novel OXA enzymes were identified, OXA-235 in 8 isolates and the amino acid variants OXA-236 (Glu173-Val) and OXA-237 (Asp208-Gly) in 1 isolate each. The deduced amino acid sequences shared 85% identity with OXA-134, 54% to 57% identities with the acquired OXA-23, OXA-24, OXA-58, and OXA-143, and 56% identity with the intrinsic OXA-51 and, thus, represent a novel subclass of OXA. The expression of OXA-235 inA. baumanniiled to reduced carbapenem susceptibility, while cephalosporin MICs were unaffected. Genetic analysis revealed thatblaOXA-235,blaOXA-236, andblaOXA-237were bracketed between two ISAba1insertion sequences. In addition, the presence of these acquired β-lactamase genes might result from a transposition-mediated mechanism. This highlights the propensity ofA. baumanniito acquire multiple carbapenem resistance determinants.

scholarly journals A New Clone Sweeps Clean: the Enigmatic Emergence of Escherichia coli Sequence Type 131

2014 ◽  
Vol 58 (9) ◽  
pp. 4997-5004 ◽  
Author(s):  
Ritu Banerjee ◽  
James R. Johnson
Keyword(s):  
Escherichia Coli ◽  
Sequence Type ◽  
Rapid Expansion ◽  
Future Research ◽  
Content Type ◽  
Extended Spectrum Beta Lactamase ◽  
E Coli ◽  
Phylogenetic Studies ◽  
Ecological Success

ABSTRACTEscherichia colisequence type 131 (ST131) is an extensively antimicrobial-resistantE. coliclonal group that has spread explosively throughout the world. Recent molecular epidemiologic and whole-genome phylogenetic studies have elucidated the fine clonal structure of ST131, which comprises multiple ST131 subclones with distinctive resistance profiles, including the (nested) H30, H30-R, and H30-Rx subclones. The most prevalent ST131 subclone, H30, arose from a single common fluoroquinolone (FQ)-susceptible ancestor containing allele 30 offimH(type 1 fimbrial adhesin gene). An early H30 subclone member acquired FQ resistance and launched the rapid expansion of the resulting FQ-resistant subclone, H30-R. Subsequently, a member of H30-R acquired the CTX-M-15 extended-spectrum beta-lactamase and launched the rapid expansion of the CTX-M-15-containing subclone within H30-R, H30-Rx. Clonal expansion clearly is now the dominant mechanism for the rising prevalence of both FQ resistance and CTX-M-15 production in ST131 and inE. coligenerally. Reasons for the successful dissemination and expansion of the key ST131 subclones remain undefined but may include increased transmissibility, greater ability to colonize and/or persist in the intestine or urinary tract, enhanced virulence, and more-extensive antimicrobial resistance compared to otherE. coli. Here we discuss the epidemiology and molecular phylogeny of ST131 and its key subclones, possible mechanisms for their ecological success, implications of their widespread dissemination, and future research needs.

scholarly journals Complete Genome Sequence of Community-Associated Methicillin-Resistant Staphylococcus aureus Sequence Type 1, SCC mec IV[2B], Isolated in the 1990s from Northern Western Australia

2021 ◽  
Vol 10 (37) ◽  
Author(s):  
Nicola M. Karakatsanis ◽  
Shakeel Mowlaboccus ◽  
Elena Colombi ◽  
Julie C. Pearson ◽  
Joshua P. Ramsay ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Genome Sequence ◽  
Western Australia ◽  
Complete Genome Sequence ◽  
Complete Genome ◽  
Sequence Type ◽  
Indigenous Australian ◽  
Methicillin Resistant ◽  
Content Type

Sequence type 1 (ST1) methicillin-resistant Staphylococcus aureus (MRSA) type IV[2B] has become one of the most common community-associated MRSA clones in Australia. We report the complete genome sequence of one of the earliest isolated Australian S. aureus ST1-MRSA-IV strains, WBG8287, isolated from an Indigenous Australian patient living in the remote Kimberley Region of Western Australia.

scholarly journals Ceftazidime-Avibactam Resistance Mediated by the N346Y Substitution in Various AmpC β-Lactamases

2020 ◽  
Vol 64 (6) ◽  
Author(s):  
Fabrice Compain ◽  
Agathe Debray ◽  
Pauline Adjadj ◽  
Delphine Dorchêne ◽  
Michel Arthur
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Amino Acid ◽  
Resistance Mechanism ◽  
Enterobacter Cloacae ◽  
Common Mechanism ◽  
Citrobacter Freundii ◽  
Content Type ◽  
Hydrogen Interaction ◽  
Y Substitution ◽  
Lactamase Inhibitor

ABSTRACT Chromosomal and plasmid-borne AmpC cephalosporinases are a major resistance mechanism to β-lactams in Enterobacteriaceae and Pseudomonas aeruginosa. The new β-lactamase inhibitor avibactam effectively inhibits class C enzymes and can fully restore ceftazidime susceptibility. The conserved amino acid residue Asn346 of AmpC cephalosporinases directly interacts with the avibactam sulfonate. Disruption of this interaction caused by the N346Y amino acid substitution in Citrobacter freundii AmpC was previously shown to confer resistance to the ceftazidime-avibactam combination (CAZ-AVI). The aim of this study was to phenotypically and biochemically characterize the consequences of the N346Y substitution in various AmpC backgrounds. Introduction of N346Y into Enterobacter cloacae AmpC (AmpCcloacae), plasmid-mediated DHA-1, and P. aeruginosa PDC-5 led to 270-, 12,000-, and 79-fold decreases in the inhibitory efficacy (k2/Ki) of avibactam, respectively. The kinetic parameters of AmpCcloacae and DHA-1 for ceftazidime hydrolysis were moderately affected by the substitution. Accordingly, AmpCcloacae and DHA-1 harboring N346Y conferred CAZ-AVI resistance (MIC of ceftazidime of 16 μg/ml in the presence of 4 μg/ml of avibactam). In contrast, production of PDC-5 N346Y was associated with a lower MIC (4 μg/ml) since this β-lactamase retained a higher inactivation efficacy by avibactam in comparison to AmpCcloacae N346Y. For FOX-3, the I346Y substitution did not reduce the inactivation efficacy of avibactam and the substitution was highly deleterious for β-lactam hydrolysis, including ceftazidime, preventing CAZ-AVI resistance. Since AmpCcloacae and DHA-1 display substantial sequence diversity, our results suggest that loss of hydrogen interaction between Asn346 and avibactam could be a common mechanism of acquisition of CAZ-AVI resistance.

Susceptibility to type 1 autoimmune hepatitis is associated with shared amino acid sequences at positions 70–74 of the HLA-DRB1 molecule

2008 ◽  
Vol 48 (1) ◽  
pp. 133-139 ◽  
Author(s):  
Young-Suk Lim ◽  
Heung-Bum Oh ◽  
Sung-Eun Choi ◽  
Oh-Joong Kwon ◽  
Yong-Seok Heo ◽  
...  
Keyword(s):  
Amino Acid ◽  
Autoimmune Hepatitis ◽  
Amino Acid Sequences

scholarly journals IgA proteases of two distinct specificities are released by Neisseria meningitidis.

1980 ◽  
Vol 152 (5) ◽  
pp. 1442-1447 ◽  
Author(s):  
M H Mulks ◽  
A G Plaut ◽  
H A Feldman ◽  
B Frangione
Keyword(s):  
Amino Acid ◽  
Neisseria Meningitidis ◽  
Heavy Chain ◽  
Peptide Bond ◽  
Amino Acid Sequences ◽  
Hinge Region ◽  
Amino Terminal ◽  
Group A

Strains of Neisseria meningitidis produce two distinct extracellular IgA proteases that cleave the human IgA1 heavy chain at different points within the hinge region. Type 1 protease cleaves the prolyl-seryl peptide bond at position 237-238; type type 2 protease cleaves the prolyl-threonyl bond two residues amino terminal to that bond attacked by type 1 enzyme. Each meningococcal isolate elaborates only one of these two enzymes, and the type of protease produced correlates with certain serogroups: group A yielding only type 1, and groups X and Y only type 2 enzyme. In addition, analysis of amino acid sequences of human alpha-chain proteins reveals that the repeating octapeptide characteristic of the IgA1 hinge region is actually triplicated.

scholarly journals Acquisition of Extended-Spectrum β-Lactamase GES-6 Leading to Resistance to Ceftolozane-Tazobactam Combination in Pseudomonas aeruginosa

2018 ◽  
Vol 63 (1) ◽  
Author(s):  
Laurent Poirel ◽  
José-Manuel Ortiz De La Rosa ◽  
Nicolas Kieffer ◽  
Véronique Dubois ◽  
Aurélie Jayol ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Amino Acid ◽  
Hydrolytic Activity ◽  
Sequence Type ◽  
Effective Alternative ◽  
Amino Acid Substitutions ◽  
Content Type ◽  
Extended Spectrum

ABSTRACT A clinical Pseudomonas aeruginosa isolate resistant to all β-lactams, including ceftolozane-tazobactam and carbapenems, was recovered. It belonged to sequence type 235 and produced the extended-spectrum β-lactamase (ESBL) GES-6 differing from GES-1 by two amino acid substitutions (E104K and G170S). GES-6 possessed an increased hydrolytic activity toward carbapenems and to ceftolozane and a decreased susceptibility to β-lactamase inhibitors compared to GES-1, except for avibactam. We show here that resistance to ceftolozane-tazobactam may occur through acquisition of a specific ESBL in P. aeruginosa but that ceftazidime-avibactam combination remains an effective alternative.

scholarly journals In silico prediction of the functional and structural consequences of the non-synonymous single nucleotide polymorphism A122V in bovine CXC chemokine receptor type 1

2020 ◽  
Vol 80 (1) ◽  
pp. 39-46
Author(s):  
A. F. Guzzi ◽  
F. S. L. Oliveira ◽  
M. M. S. Amaro ◽  
P. F. Tavares-Filho ◽  
J. E. Gabriel
Keyword(s):  
Amino Acid ◽  
Chemokine Receptor ◽  
In Silico ◽  
Alpha Helix ◽  
Amino Acid Sequences ◽  
Receptor Type ◽  
Amino Acid Residues ◽  
Causal Polymorphism ◽  
Cxc Chemokine

Abstract The current study aimed to assess whether the A122V causal polymorphism promotes alterations in the functional and structural proprieties of the CXC chemokine receptor type 1 protein (CXCR1) of cattle Bos taurus by in silico analyses. Two amino acid sequences of bovine CXCR1 was selected from database UniProtKB/Swiss-Prot: a) non-polymorphic sequence (A7KWG0) with alanine (A) at position 122, and b) polymorphic sequence harboring the A122V polymorphism, substituting alanine by valine (V) at same position. CXCR1 sequences were submitted as input to different Bioinformatics’ tools to examine the effects of this polymorphism on functional and structural stabilities, to predict eventual alterations in the 3-D structural modeling, and to estimate the quality and accuracy of the predictive models. The A122V polymorphism exerted tolerable and non-deleterious effects on the polymorphic CXCR1, and the predictive structural model for polymorphic CXCR1 revealed an alpha helix spatial structure typical of a receptor transmembrane polypeptide. Although higher variations in the distances between pairs of amino acid residues at target-positions are detected in the polymorphic CXCR1 protein, more than 97% of the amino acid residues in both models were located in favored and allowed conformational regions in Ramachandran plots. Evidences has supported that the A122V polymorphism in the CXCR1 protein is associated with increased clinical mastitis incidence in dairy cows. Thus, the findings described herein prove that the replacement of the alanine by valine amino acids provokes local conformational changes in the A122V-harboring CXCR1 protein, which could directly affect its post-translational folding mechanisms and biological functionality.

scholarly journals CYP101J2, CYP101J3, and CYP101J4, 1,8-Cineole-Hydroxylating Cytochrome P450 Monooxygenases from Sphingobium yanoikuyae Strain B2

2016 ◽  
Vol 82 (22) ◽  
pp. 6507-6517 ◽  
Author(s):  
Birgit Unterweger ◽  
Dieter M. Bulach ◽  
Judith Scoble ◽  
David J. Midgley ◽  
Paul Greenfield ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Amino Acid ◽  
Amino Acid Sequences ◽  
Cytochrome P450 Monooxygenases ◽  
Content Type ◽  
E Coli ◽  
P450 Monooxygenases ◽  
Isolation And Characterization ◽  
Starting Point

ABSTRACTWe report the isolation and characterization of three new cytochrome P450 monooxygenases: CYP101J2, CYP101J3, and CYP101J4. These P450s were derived fromSphingobium yanoikuyaeB2, a strain that was isolated from activated sludge based on its ability to fully mineralize 1,8-cineole. Genome sequencing of this strain in combination with purification of native 1,8-cineole-binding proteins enabled identification of 1,8-cineole-binding P450s. The P450 enzymes were cloned, heterologously expressed (N-terminally His6tagged) inEscherichia coliBL21(DE3), purified, and spectroscopically characterized. Recombinant whole-cell biotransformation inE. colidemonstrated that all three P450s hydroxylate 1,8-cineole using electron transport partners fromE. colito yield a product putatively identified as (1S)-2α-hydroxy-1,8-cineole or (1R)-6α-hydroxy-1,8-cineole. The new P450s belong to the CYP101 family and share 47% and 44% identity with other 1,8-cineole-hydroxylating members found inNovosphingobium aromaticivoransandPseudomonas putida. Compared to P450cin(CYP176A1), a 1,8-cineole-hydroxylating P450 fromCitrobacter braakii, these enzymes share less than 30% amino acid sequence identity and hydroxylate 1,8-cineole in a different orientation. Expansion of the enzyme toolbox for modification of 1,8-cineole creates a starting point for use of hydroxylated derivatives in a range of industrial applications.IMPORTANCECYP101J2, CYP101J3, and CYP101J4 are cytochrome P450 monooxygenases fromS. yanoikuyaeB2 that hydroxylate the monoterpenoid 1,8-cineole. These enzymes not only play an important role in microbial degradation of this plant-based chemical but also provide an interesting route to synthesize oxygenated 1,8-cineole derivatives for applications as natural flavor and fragrance precursors or incorporation into polymers. The P450 cytochromes also provide an interesting basis from which to compare other enzymes with a similar function and expand the CYP101 family. This could eventually provide enough bacterial parental enzymes with similar amino acid sequences to enablein vitroevolution via DNA shuffling.

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