scholarly journals WGS of Commensal Neisseria Reveals Acquisition of a New Ribosomal Protection Protein (MsrD) as a Possible Explanation for High Level Azithromycin Resistance in Belgium

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 384
Author(s):  
Tessa de Block ◽  
Jolein Gyonne Elise Laumen ◽  
Christophe Van Dijck ◽  
Said Abdellati ◽  
Irith De Baetselier ◽  
...  
Keyword(s):  
Integration Site ◽  
Bacterial Species ◽  
Resistance Mechanism ◽  
Health Concern ◽  
Sex With Men ◽  
High Level ◽  
Ribosomal Protection Protein ◽  
Commensal Neisseria ◽  
Level Resistance ◽  
Ribosomal Protection

In this study, we characterized all oropharyngeal and anorectal isolates of Neisseria spp. in a cohort of men who have sex with men. This resulted in a panel of pathogenic Neisseria (N. gonorrhoeae [n = 5] and N. meningitidis [n = 5]) and nonpathogenic Neisseria (N. subflava [n = 11], N. mucosa [n = 3] and N. oralis [n = 2]). A high proportion of strains in this panel were resistant to azithromycin (18/26) and ceftriaxone (3/26). Whole genome sequencing (WGS) of these strains identified numerous mutations that are known to confer reduced susceptibility to azithromycin and ceftriaxone in N. gonorrhoeae. The presence or absence of these known mutations did not explain the high level resistance to azithromycin (>256 mg/L) in the nonpathogenic isolates (8/16). After screening for antimicrobial resistance (AMR) genes, we found a ribosomal protection protein, Msr(D), in these highly azithromycin resistant nonpathogenic strains. The complete integration site originated from Streptococcus pneumoniae and is associated with high level resistance to azithromycin in many other bacterial species. This novel AMR resistance mechanism to azithromycin in nonpathogenic Neisseria could be a public health concern if it were to be transmitted to pathogenic Neisseria. This study demonstrates the utility of WGS-based surveillance of nonpathogenic Neisseria.

scholarly journals Phenotypic Characterization of Two Ancylostoma caninum Isolates with Different Susceptibilities to the Anthelmintic Pyrantel

2008 ◽  
Vol 52 (11) ◽  
pp. 3980-3986 ◽  
Author(s):  
Steven R. Kopp ◽  
Glen T. Coleman ◽  
James S. McCarthy ◽  
Andrew C. Kotze
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Resistance Mechanism ◽  
Fold Increase ◽  
Phenotypic Characterization ◽  
Gastrointestinal Helminths ◽  
Ancylostoma Caninum ◽  
High Level ◽  
Level Resistance

ABSTRACT The anthelmintic pyrantel plays an important role in the control of gastrointestinal helminths of humans and domestic animals. Despite the demonstration of pyrantel resistance in several helminth species over the last 20 years, the resistance mechanism remains unclear. It has been hypothesized that resistance may arise as a consequence of changes to the relative proportions of subpopulations of nicotinic acetylcholine receptors (nAchRs). To test this hypothesis, we examined the responses of two isolates of the canine hookworm Ancylostoma caninum with low-level resistance (isolate NT) and high-level resistance (isolate PR) to pyrantel to nicotinic agonist drugs reported to be selective for three nAchR subtypes. We used larval motility and conformation assays and force transduction experiments with adult worms. Pyrantel and levamisole were less potent against larvae of isolate PR than larvae of isolate NT (up to an 18-fold increase in the 50% inhibitory concentration); on the other hand, bephenium was more potent against larvae of isolate PR than larvae of isolate NT (twofold) and nicotine had the same potency against larvae of both isolates. In adults, pyrantel, levamisole, and nicotine were less potent against isolate PR than isolate NT (two- to threefold), but the potency of bephenium against the two isolates was equivalent. Our data indicate a complex pattern of nAchRs in this species and suggest that the two isolates differ in their relative sensitivities to agonists targeting different nAchRs.

scholarly journals Sequence Analysis of the gyrA andparC Homologues of a Wild-Type Strain of Vibrio parahaemolyticus and Its Fluoroquinolone-Resistant Mutants

1999 ◽  
Vol 43 (5) ◽  
pp. 1156-1162 ◽  
Author(s):  
Jun Okuda ◽  
Eriko Hayakawa ◽  
Mitsuaki Nishibuchi ◽  
Takeshi Nishino
Keyword(s):  
Vibrio Parahaemolyticus ◽  
Resistance Mechanism ◽  
Point Mutations ◽  
Erwinia Carotovora ◽  
Open Reading Frames ◽  
Fluoroquinolone Resistance ◽  
Degenerate Primers ◽  
Resistant Mutants ◽  
High Level ◽  
Level Resistance

ABSTRACT Vibrio parahaemolyticus causes seafood-borne gastroenteritis in humans. It is particularly important in Japan, where raw seafood is frequently consumed. Fluoroquinolone is one of the current drugs of choice for treating patients infected by V. parahaemolyticus because resistant strains are rarely found. To study a possible fluoroquinolone resistance mechanism in this organism, nucleotide sequences that are homologous to known gyrA andparC genes have been cloned from V. parahaemolyticus AQ3815 and sequenced by amplification with degenerate primers of the quinolone resistance-determining region (QRDR), followed by cassette ligation-mediated PCR. Open reading frames encoding polypeptides of 878 and 761 amino acid residues were detected in the gyrA and parC homologues, respectively. The V. parahaemolyticus GyrA and ParC sequences were most closely related to Erwinia carotovora GyrA (76% identity) and Escherichia coli ParC (69% identity) sequences, respectively. Ciprofloxacin-resistant mutants of AQ3815 were obtained on an agar medium by multistep selection with increasing levels of the quinolone. One point mutation only in the gyrA QRDR was detected among mutants with low- to intermediate-level resistance, while point mutations in both the gyrA and parCQRDRs were detected only in strains with high-level resistance. These results strongly suggest that, as in other gram-negative bacteria, GyrA and ParC are the primary and secondary targets, respectively, of ciprofloxacin in V. parahaemolyticus.

scholarly journals Characterization of an Enterococcus gallinarum Isolate Carrying a DualvanAandvanBCassette

2015 ◽  
Vol 53 (7) ◽  
pp. 2225-2229 ◽  
Author(s):  
Alireza Eshaghi ◽  
Dea Shahinas ◽  
Aimin Li ◽  
Ruwandi Kariyawasam ◽  
Philip Banh ◽  
...  
Keyword(s):  
Clinical Isolate ◽  
Resistance Mechanism ◽  
Vancomycin Resistance ◽  
Content Type ◽  
Enterococcal Species ◽  
Enterococcus Gallinarum ◽  
High Level ◽  
Identification And Characterization ◽  
Level Resistance

The ability of vancomycin resistance determinants to be horizontally transferred within enterococci species is a concern. Identification and characterization of vancomycin-resistant enterococci (VRE) in a clinical isolate have a significant impact on infection control practices. In this study, we describe a clinical isolate ofEnterococcus gallinarumexhibiting high-level resistance to vancomycin and teicoplanin. The genetic characterization of this isolate showed the presence ofvanAandvanBgenes in addition to the naturally carriedvanCgene.vanAwas identified on pA6981, a 35,608-bp circular plasmid with significant homology to plasmid pS177. ThevanBoperon was integrated into the bacterial chromosome and showed a high level of homology to previously reported Tn1549and Tn5382. To the best of our knowledge, this is the first report ofE. gallinarumcarrying bothvanAandvanBoperons, indicating the importance of identifying the vancomycin resistance mechanism in non-E. faeciumand non-E. faecalisenterococcal species.

scholarly journals Resistance to Glycopeptide Antibiotics in the Teicoplanin Producer Is Mediated by van Gene Homologue Expression Directing the Synthesis of a Modified Cell Wall Peptidoglycan

2007 ◽  
Vol 51 (4) ◽  
pp. 1135-1141 ◽  
Author(s):  
Fabrizio Beltrametti ◽  
Arianna Consolandi ◽  
Lucia Carrano ◽  
Francesca Bagatin ◽  
Roberta Rossi ◽  
...  
Keyword(s):  
Cell Wall ◽  
Resistance Mechanism ◽  
Gene Clusters ◽  
Glycopeptide Antibiotics ◽  
Constitutive Analysis ◽  
High Concentrations ◽  
High Level ◽  
Gene Homologue ◽  
Level Resistance ◽  
Comprehensive Study

ABSTRACT Glycopeptide resistance has been studied in detail in enterococci and staphylococci. In these microorganisms, high-level resistance is achieved by replacing the C-terminal d-alanyl-d-alanine of the nascent peptidoglycan with d-alanyl-d-lactate or d-alanyl-d-serine, thus reducing the affinities of glycopeptides for cell wall targets. Reorganization of the cell wall is directed by the expression of the van gene clusters. The identification of van gene homologs in the genomes of several glycopeptide-producing actinomycetes suggests the involvement of a similar self-resistance mechanism to avoid suicide. This report describes a comprehensive study of self-resistance in Actinoplanes teichomyceticus ATCC 31121, the producer of the clinically relevant glycopeptide teicoplanin. A. teichomyceticus ATCC 31121 showed a MIC of teicoplanin of 25 μg/ml and a MIC of vancomycin of 90 μg/ml during vegetative growth. The vanH, vanA, and vanX genes of A. teichomyceticus were found to be organized in an operon whose transcription was constitutive. Analysis of the UDP-linked peptidoglycan precursors revealed the presence of UDP-glycomuramyl pentadepsipeptide terminating in d-alanyl-d-lactate. No trace of precursors ending in d-alanyl-d-alanine was detected. Thus, the van gene complex was transcribed and expressed in the genetic background of A. teichomyceticus and conferred resistance to vancomycin and teicoplanin through the modification of cell wall biosynthesis. During teicoplanin production (maximum productivity, 70 to 80 μg/ml), the MIC of teicoplanin remained in the range of 25 to 35 μg/ml. Teicoplanin-producing cells were found to be tolerant to high concentrations of exogenously added glycopeptides, which were not bactericidal even at 5,000 μg/ml.

scholarly journals Resistance of Saccharomyces cerevisiae to High Concentrations of Furfural Is Based on NADPH-Dependent Reduction by at Least Two Oxireductases

2009 ◽  
Vol 75 (24) ◽  
pp. 7631-7638 ◽  
Author(s):  
Dominik Heer ◽  
Daniel Heine ◽  
Uwe Sauer
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Defense Mechanism ◽  
Resistance Mechanism ◽  
Pentose Phosphate ◽  
Process Conditions ◽  
Transcript Analysis ◽  
Reading Frame ◽  
High Concentrations ◽  
High Level ◽  
Level Resistance

ABSTRACT Biofuels derived from lignocellulosic biomass hold promises for a sustainable fuel economy, but several problems hamper their economical feasibility. One important problem is the presence of toxic compounds in processed lignocellulosic hydrolysates, with furfural as a key toxin. While Saccharomyces cerevisiae has some intrinsic ability to reduce furfural to the less-toxic furfuryl alcohol, higher resistance is necessary for process conditions. By comparing an evolved, furfural-resistant strain and its parent in microaerobic, glucose-limited chemostats at increasing furfural challenge, we elucidate key mechanism and the molecular basis of both natural and high-level furfural resistance. At lower concentrations of furfural, NADH-dependent oxireductases are the main defense mechanism. At furfural concentrations above 15 mM, however, 13C-flux and global array-based transcript analysis demonstrated that the NADPH-generating flux through the pentose phosphate pathway increases and that NADPH-dependent oxireductases become the major resistance mechanism. The transcript analysis further revealed that iron transmembrane transport is upregulated in response to furfural. While these responses occur in both strains, high-level resistance in the evolved strain was based on strong induction of ADH7, the uncharacterized open reading frame (ORF) YKL071W, and four further, likely NADPH-dependent, oxireductases. By overexpressing the ADH7 gene and the ORF YKL071W, we inversely engineered significantly increased furfural resistance in the parent strain, thereby demonstrating that these two enzymes are key elements of the resistance phenotype.

scholarly journals Long-Term Shifts in Patterns of Antibiotic Resistance in Enteric Bacteria

2000 ◽  
Vol 66 (12) ◽  
pp. 5406-5409 ◽  
Author(s):  
Tara Houndt ◽  
Howard Ochman
Keyword(s):  
Antibiotic Resistance ◽  
Bacterial Species ◽  
Natural Populations ◽  
Enteric Bacteria ◽  
Commercial Application ◽  
Before And After ◽  
Resistance Patterns ◽  
High Level ◽  
Antibiotic Resistance Patterns ◽  
Level Resistance

ABSTRACT Several mechanisms are responsible for the ability of microorganisms to tolerate antibiotics, and the incidence of resistance to these compounds within bacterial species has increased since the commercial use of antibiotics became widespread. To establish the extent of and changes in the diversity of antibiotic resistance patterns in natural populations, we determined the MICs of five antibiotics for collections of enteric bacteria isolated from diverse hosts and geographic locations and during periods before and after commercial application of antibiotics began. All of the pre-antibiotic era strains were susceptible to high levels of these antibiotics, whereas 20% of strains from contemporary populations ofEscherichia coli and Salmonella entericadisplayed high-level resistance to at least one of the antibiotics. In addition to the increase in the frequency of high-level resistance, background levels, conferred by genes providing nonspecific low-level resistance to multiple antibiotics, were significantly higher among contemporary strains. Changes in the incidence and levels of antibiotic resistance are not confined to particular segments of the bacterial population and reflect responses to the increased exposure of bacteria to antimicrobial compounds over the past several decades.

scholarly journals Current antimicrobial sensitivity pattern of typhoidal salmonellae in a referral diagnostic centre

2016 ◽  
Vol 31 (1) ◽  
Author(s):  
Umer Shujat ◽  
Aamer Ikram ◽  
Inam Qadir Javaid Hashmi ◽  
Shahid Ahmed Abbasi ◽  
Amna Afzal ◽  
...  
Keyword(s):  
Health Concern ◽  
Third Generation ◽  
Susceptibility Pattern ◽  
Marked Rise ◽  
Antimicrobial Sensitivity ◽  
Sensitivity Pattern ◽  
High Level ◽  
Third Generation Cephalosporins ◽  
Diagnostic Centre ◽  
Level Resistance

Background: Infections caused by typhoidal salmonellae are an important public health concern in Pakistan. Inappropriate and injudicious use of fluoroquinolones has reduced their efficacy due to development of high level resistance. <br />Aim: To ascertain the current susceptibility pattern of typhoidal salmonellae thus guiding the physicians for better management of typhoid patients.<br />Materials and Methods: A study was conducted at our institution from January 2012 through December 2013 to investigate current susceptibility pattern of typhoidal salmonellae. <br />Results: Out of 200 isolates, 107 (53.5%) were identified as <em>Salmonella</em> Typhi and 93 (46.5%) as <em>Salmonella</em> Paratyphi A. Sensitivities of <em>Salmonella</em> Typhi were as follows: ampicillin (48.6%), chloramphenicol (45.8%), co-trimoxazole (40.1%), ciprofloxacin (11.2%). Sensitivities of <em>Salmonella</em> Paratyphi A were: ampicillin (80.6%), chloramphenicol (89.2%), co-trimoxazole (90.3%), and ciprofloxacin (16.1%). No resistance was detected against third generation cephalosporins. <br />Conclusions: Typhoidal salmonellae are still entirely susceptible to third generation cephalosporins in our setting. Marked rise in resistance to fluoroquinolones has reduced their empirical usage. Sensitivity of <em>Salmonella</em> Paratyphi A to conventional antityphoid drugs was encouraging.

scholarly journals Phenotypic and genetic barriers to establishment of horizontally transferred genes encoding ribosomal protection proteins

2021 ◽  
Author(s):  
Kavita Yadav ◽  
Linnéa Garoff ◽  
Douglas L Huseby ◽  
Diarmaid Hughes
Keyword(s):  
Tetracycline Resistance ◽  
Nucleotide Composition ◽  
E Coli ◽  
Low Level ◽  
Wide Range ◽  
Genetic Barriers ◽  
Genes Encoding ◽  
High Level ◽  
Level Resistance ◽  
Ribosomal Protection

Abstract Background Ribosomal protection proteins (RPPs) interact with bacterial ribosomes to prevent inhibition of protein synthesis by tetracycline. RPP genes have evolved from a common ancestor into at least 12 distinct classes and spread by horizontal genetic transfer into a wide range of bacteria. Many bacterial genera host RPP genes from multiple classes but tet(M) is the predominant RPP gene found in Escherichia coli. Objectives We asked whether phenotypic barriers (low-level resistance, high fitness cost) might constrain the fixation of other RPP genes in E. coli. Methods We expressed a diverse set of six different RPP genes in E. coli, including tet(M), and quantified tetracycline susceptibility and growth phenotypes as a function of expression level, and evolvability to overcome identified phenotypic barriers. Results The genes tet(M) and tet(Q) conferred high-level tetracycline resistance without reducing fitness; tet(O) and tet(W) conferred high-level resistance but significantly reduced growth fitness; tetB(P) conferred low-level resistance and while mutants conferring high-level resistance were selectable these had reduced growth fitness; otr(A) did not confer resistance and resistant mutants could not be selected. Evolution experiments suggested that codon usage patterns in tet(O) and tet(W), and transcriptional silencing associated with nucleotide composition in tetB(P), accounted for the observed phenotypic barriers. Conclusions With the exception of tet(Q), the data reveal significant phenotypic and genetic barriers to the fixation of additional RPP genes in E. coli.

scholarly journals Persistence of an outbreak of gonorrhoea with high-level resistance to azithromycin in England, November 2014‒May 2018

2018 ◽  
Vol 23 (23) ◽  
Author(s):  
Christa Smolarchuk ◽  
Adrian Wensley ◽  
Simon Padfield ◽  
Helen Fifer ◽  
Andrew Lee ◽  
...  
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Sexual Networks ◽  
Sex With Men ◽  
High Level ◽  
Level Resistance

Between November 2014 and May 2018, 118 laboratory-confirmed cases of high-level azithromycin resistant Neisseria gonorrhoeae were identified in England. Cases emerged among heterosexuals in Leeds but spread across England and into sexual networks of men who have sex with men as the outbreak progressed. The few epidemiological links identified indicate substantial under-diagnosis of cases and this, along with the upturn in cases in 2017, highlights the difficulties in controlling the outbreak.

scholarly journals 634 Mechanism and Stability of Virus Resistance in Transgenic Papaya

HortScience ◽  
1999 ◽  
Vol 34 (3) ◽  
pp. 557A-557
Author(s):  
Richard Manshardt ◽  
Dennis Gonsalves
Keyword(s):  
New York ◽  
Protein Gene ◽  
Resistance Mechanism ◽  
Local Strains ◽  
Transgenic Papaya ◽  
Challenge Virus ◽  
Loss Of Resistance ◽  
High Level ◽  
Virus Strains ◽  
Level Resistance

Transgenic papaya line 55-1 with resistance to papaya ringspot virus (PRSV) originated in 1989 by particle bombardment of cultivar Sunset with the coat protein gene (cp) of mild mutant Hawaii PRSV strain HA 5-1. Hemizygous (+/cp) R0 clones of 55-1 displayed resistance to the virulent Hawaii HA strain in greenhouse tests in New York in 1991 and to local strains in a field trial in Hawaii from 1992 to 1994. In the R1 generation produced by crossing the pistillate R0 55-1 with `Sunset', up to 50% of the hemizygous transgenic segregants were susceptible to a local Oahu PRSV strain when inoculated as seedlings but not as mature plants. Similar inoculation experiments in New York showed that hemizygous R1 transgenics were susceptible in differing degrees to PRSV strains from regions other than Hawaii. Homozygous (cp/cp) R2, R3, and R4 populations planted in various locations in Hawaii since 1994 have consistently demonstrated high-level resistance to local strains at all stages of development. When inoculated in New York with eight non-Hawaii PRSV strains, homozygous R3 seedlings were resistant to all but a Thai strain. Transgenic resistance is the result of a complex interaction involving the stage of plant development, transgene dosage, the degree of homology between transgene and challenge virus, and environmental variables. Papaya plants transformed with nontranslatable versions of various cp genes are also highly resistant to PRSV, indicating that the resistance mechanism operates at the RNA level. No loss of resistance due to the appearance of resistance-breaking virus strains or to transgene inactivation has been noted thus far.

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