High-Level Resistance to Cobalt and Nickel but Probably No Transenvelope Efflux: Metal Resistance in the Cuban Serratia marcescens Strain C-1

2006 ◽  
Vol 53 (1) ◽  
pp. 123-133 ◽  
Author(s):  
Jeannette Marrero ◽  
Georg Auling ◽  
Orquidea Coto ◽  
Dietrich H. Nies
Keyword(s):  
Serratia Marcescens ◽  
Metal Resistance ◽  
High Level ◽  
Level Resistance ◽  
Cobalt And Nickel

High-Level Resistance to Cobalt and Nickel in Cuban Serratia marcescens Strains Isolated from Serpentine Deposits

2007 ◽  
Vol 20-21 ◽  
pp. 521-525
Author(s):  
Jeannette Marrero ◽  
Georg Auling ◽  
Orquidea Coto ◽  
Dietrich Nies
Keyword(s):  
Serratia Marcescens ◽  
Molecular Mechanisms ◽  
Regulatory Protein ◽  
Metal Resistance ◽  
Uptake System ◽  
Nickel Resistance ◽  
16S Rrna Analysis ◽  
E Coli ◽  
Flow Equilibrium ◽  
Cobalt And Nickel

A collection of highly nickel and cobalt-resistant enterobacteria were isolated from the Punta Gorda serpentine deposit (Moa, Cuba). The most nickel and cobalt resistant strain (termed C- 1) was assigned to Serratia marcescens by 16S rRNA analysis and DNA/DNA hybridization and the molecular mechanisms underlying its inducible cobalt and nickel resistance was investigated. Genes involved in metal resistance were identified by transposon mutagenesis followed by selection for Co- and Ni-sensitive derivatives. The transposon insertion causing the highest decrease in metal resistance was located in the ncrABC determinant. The three ORFs (ncrA, ncrB and ncrC) were cloned in E. coli. The predicted NcrA product was an NreB ortholog of the major facilitator protein superfamily and was central for Co/Ni resistance in S. marcescens strain C-1. NcrA also mediated metal resistance in E. coli and caused decreased accumulation of Co and Ni in this heterologous host. NcrB may be a regulatory protein. NcrC was a protein of the Ni–Co transport (NiCoT) protein family and necessary for full metal resistance in E. coli, but only when NcrA was also present. Without NcrA, NcrC caused a slight decrease in metal resistance and mediated increased accumulation of Ni and Co. As the cytoplasmic metal concentration can be assumed to be the result of a flow equilibrium of uptake and efflux processes, this interplay between metal uptake system NcrC and metal efflux system NcrA may contribute to nickel and cobalt resistance in this bacterium.

scholarly journals Mutation in Serratia marcescens AmpC β-Lactamase Producing High-Level Resistance to Ceftazidime and Cefpirome

2001 ◽  
Vol 45 (8) ◽  
pp. 2331-2339 ◽  
Author(s):  
Alessandro Raimondi ◽  
Francesca Sisto ◽  
Hiroshi Nikaido
Keyword(s):  
Serratia Marcescens ◽  
Catalytic Efficiency ◽  
Fold Increase ◽  
Mutant Enzyme ◽  
Kinetic Properties ◽  
Cloning And Sequencing ◽  
Mutant Strains ◽  
High Level ◽  
Outer Membrane Permeability ◽  
Level Resistance

ABSTRACT Starting from a clinical isolate of Serratia marcescens that produced a chromosomally encoded AmpC β-lactamase inducibly, we isolated by stepwise selection two laboratory mutants that showed high levels of resistance to some cephalosporins. The 98R mutant apparently overproduced the unaltered β-lactamase constitutively, but the 520R mutant produced an altered enzyme, also constitutively. Ceftazidime and cefpirome MICs for the 520R mutant were much higher (512 and 64 μg/ml, respectively) than those for the 98R mutant (16 and 16 μg/ml, respectively). Yet the MICs of cephaloridine and piperacillin for the 520R mutant were four- to eightfold lower than those for the 98R mutant. Cloning and sequencing of theampC alleles showed that in the 520R mutant enzyme, the Thr64 residue, about two turns away from the active-site serine, was mutated to isoleucine. This resulted in a >1,000-fold increase in the catalytic efficiency (k cat/K m ) of the mutated AmpC enzyme toward ceftazidime, whereas there was a >10-fold decrease in the efficiency of the mutant enzyme toward cefazolin and cephaloridine. The outer membrane permeability of the 520R strain to cephalosporins was also less than in the 98R strain, and the alteration of the kinetic properties of the AmpC enzyme together with this difference in permeability explained quantitatively the resistance levels of both mutant strains to most agents studied.

scholarly journals Resistance to Cefepime and Cefpirome Due to a 4-Amino-Acid Deletion in the Chromosome-Encoded AmpC β-Lactamase of a Serratia marcescens Clinical Isolate

2004 ◽  
Vol 48 (3) ◽  
pp. 716-720 ◽  
Author(s):  
Hedi Mammeri ◽  
Laurent Poirel ◽  
Pascal Bemer ◽  
Henri Drugeon ◽  
Patrice Nordmann
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract Infection ◽  
Amino Acid ◽  
Serratia Marcescens ◽  
Reference Strain ◽  
Sequencing Analysis ◽  
Amino Acid Deletion ◽  
Synergy Test ◽  
High Level ◽  
Level Resistance

ABSTRACT A multiresistant Serratia marcescens strain, HD, isolated from a patient with a urinary tract infection, was resistant to amino-, carboxy-, and ureidopenicillins, ceftazidime, and cefepime and was susceptible to cefotaxime and ceftriaxone, according to the guidelines of the NCCLS. No synergy was found between expanded-spectrum cephalosporins and clavulanic acid, according to the double-disk synergy test. The bla AmpC gene of the strain was amplified by PCR and cloned into Escherichia coli DH10B, giving rise to high-level resistance to ceftazidime, cefepime, and cefpirome. Sequencing analysis revealed that the bla AmpC gene from S. marcescens HD had a 12-nucleotide deletion compared to the bla AmpC gene from reference strain S. marcescens S3, leading to a 4-amino-acid deletion located in the H-10 helix of the β-lactamase. Kinetic analysis showed that this enzyme significantly hydrolyzed ceftazidime, cefepime, and cefpirome. This work underlined that resistance to the latest expanded-spectrum cephalosporins may be mediated by structurally modified AmpC-type β-lactamases.

The Chemistry of Drugs to Treat Candida albicans

2019 ◽  
Vol 19 (28) ◽  
pp. 2554-2566 ◽  
Author(s):  
Aurelio Ortiz ◽  
Estibaliz Sansinenea
Keyword(s):  
Candida Species ◽  
Antifungal Drugs ◽  
New Drugs ◽  
Drug Classes ◽  
Life Threatening ◽  
Antifungal Substances ◽  
High Level ◽  
Systemic Infections ◽  
New Compounds ◽  
Level Resistance

Background:: Candida species are in various parts of the human body as commensals. However, they can cause local mucosal infections and, sometimes, systemic infections in which Candida species can spread to all major organs and colonize them. Objective:: For the effective treatment of the mucosal infections and systemic life-threatening fungal diseases, a considerably large number of antifungal drugs have been developed and used for clinical purposes that comprise agents from four main drug classes: the polyenes, azoles, echinocandins, and antimetabolites. Method: : The synthesis of some of these drugs is available, allowing synthetic modification of the molecules to improve the biological activity against Candida species. The synthetic methodology for each compound is reviewed. Results: : The use of these compounds has caused a high-level resistance against these drugs, and therefore, new antifungal substances have been described in the last years. The organic synthesis of the known and new compounds is reported. Conclusion: : This article summarizes the chemistry of the existing agents, both the old drugs and new drugs, in the treatment of infections due to C. albicans, including the synthesis of the existing drugs.

scholarly journals Mutations in fbiD (Rv2983) as a Novel Determinant of Resistance to Pretomanid and Delamanid in Mycobacterium tuberculosis

2020 ◽  
Vol 65 (1) ◽  
pp. e01948-20
Author(s):  
Dalin Rifat ◽  
Si-Yang Li ◽  
Thomas Ioerger ◽  
Keshav Shah ◽  
Jean-Philippe Lanoix ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Clinical Evidence ◽  
Clinical Samples ◽  
Loss Of Function ◽  
Wild Type ◽  
Content Type ◽  
Solid Media ◽  
High Level ◽  
Level Resistance

ABSTRACTThe nitroimidazole prodrugs delamanid and pretomanid comprise one of only two new antimicrobial classes approved to treat tuberculosis (TB) in 50 years. Prior in vitro studies suggest a relatively low barrier to nitroimidazole resistance in Mycobacterium tuberculosis, but clinical evidence is limited to date. We selected pretomanid-resistant M. tuberculosis mutants in two mouse models of TB using a range of pretomanid doses. The frequency of spontaneous resistance was approximately 10−5 CFU. Whole-genome sequencing of 161 resistant isolates from 47 mice revealed 99 unique mutations, of which 91% occurred in 1 of 5 genes previously associated with nitroimidazole activation and resistance, namely, fbiC (56%), fbiA (15%), ddn (12%), fgd (4%), and fbiB (4%). Nearly all mutations were unique to a single mouse and not previously identified. The remaining 9% of resistant mutants harbored mutations in Rv2983 (fbiD), a gene not previously associated with nitroimidazole resistance but recently shown to be a guanylyltransferase necessary for cofactor F420 synthesis. Most mutants exhibited high-level resistance to pretomanid and delamanid, although Rv2983 and fbiB mutants exhibited high-level pretomanid resistance but relatively small changes in delamanid susceptibility. Complementing an Rv2983 mutant with wild-type Rv2983 restored susceptibility to pretomanid and delamanid. By quantifying intracellular F420 and its precursor Fo in overexpressing and loss-of-function mutants, we provide further evidence that Rv2983 is necessary for F420 biosynthesis. Finally, Rv2983 mutants and other F420H2-deficient mutants displayed hypersusceptibility to some antibiotics and to concentrations of malachite green found in solid media used to isolate and propagate mycobacteria from clinical samples.

scholarly journals Molecular pathways to high-level azithromycin resistance in Neisseria gonorrhoeae

2021 ◽  
Author(s):  
J G E Laumen ◽  
S S Manoharan-Basil ◽  
E Verhoeven ◽  
S Abdellati ◽  
I De Baetselier ◽  
...  
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Ribosomal Proteins ◽  
Efflux Pump ◽  
23S Rrna ◽  
Rrna Gene ◽  
23S Rrna Gene ◽  
Evolution Of Resistance ◽  
High Level ◽  
Azithromycin Resistance ◽  
Level Resistance

Abstract Background The prevalence of azithromycin resistance in Neisseria gonorrhoeae is increasing in numerous populations worldwide. Objectives To characterize the genetic pathways leading to high-level azithromycin resistance. Methods A customized morbidostat was used to subject two N. gonorrhoeae reference strains (WHO-F and WHO-X) to dynamically sustained azithromycin pressure. We tracked stepwise evolution of resistance by whole genome sequencing. Results Within 26 days, all cultures evolved high-level azithromycin resistance. Typically, the first step towards resistance was found in transitory mutations in genes rplD, rplV and rpmH (encoding the ribosomal proteins L4, L22 and L34 respectively), followed by mutations in the MtrCDE-encoded efflux pump and the 23S rRNA gene. Low- to high-level resistance was associated with mutations in the ribosomal proteins and MtrCDE efflux pump. However, high-level resistance was consistently associated with mutations in the 23S ribosomal RNA, mainly the well-known A2059G and C2611T mutations, but also at position A2058G. Conclusions This study enabled us to track previously reported mutations and identify novel mutations in ribosomal proteins (L4, L22 and L34) that may play a role in the genesis of azithromycin resistance in N. gonorrhoeae.

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.

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