Plasmid-mediated quinolone resistance by genes qnrA1 and qnrB19 in Salmonella strains isolated in Brazil

Considering the importance of the mechanisms involved in quinolone resistance, this study evaluate the presence of PMQR in 126 epidemic and not epidemic strains of Salmonella spp. It was noted that presence of PMQR, by itself, did not generate resistance to ciprofloxacin; but detection of qnr genes in Salmonella spp. and the identification of the qnrB19 variant in a strain of poultry origin alert for the indiscriminate use of quinolones in poultry production, that can result in a pressure for mutant selection of resistant strains with a clinical limitation use of FQs in the near future. And last but not least, is the need to continued study of resistance mechanisms and to monitor the microbial resistance profile of epidemiological strains.

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In Vitro Activity of CEM-101 against Streptococcus pneumoniae and Streptococcus pyogenes with Defined Macrolide Resistance Mechanisms

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01123-09 ◽

2009 ◽

Vol 54 (1) ◽

pp. 230-238 ◽

Cited By ~ 46

Author(s):

Pamela McGhee ◽

Catherine Clark ◽

Klaudia M. Kosowska-Shick ◽

Kensuke Nagai ◽

Bonifacio Dewasse ◽

...

Keyword(s):

Streptococcus Pyogenes ◽

Bacterial Species ◽

Resistance Mechanisms ◽

Macrolide Resistance ◽

23S Rrna ◽

Resistant Strains ◽

Resistant Mutants ◽

The One ◽

Selection Of

ABSTRACT CEM-101 had MIC ranges of 0.002 to 0.016 μg/ml against macrolide-susceptible pneumococci and 0.004 to 1 μg/ml against macrolide-resistant phenotypes. Only 3 strains with erm(B), with or without mef(A), had CEM-101 MICs of 1 μg/ml, and 218/221 strains had CEM-101 MICs of ≤0.5 μg/ml. CEM-101 MICs were as much as 4-fold lower than telithromycin MICs against all strains. For Streptococcus pyogenes, CEM-101 MICs ranged from 0.008 to 0.03 μg/ml against macrolide-susceptible strains and from 0.015 to 1 μg/ml against macrolide-resistant strains. Against erm(B) strains, erythromycin, azithromycin, and clarithromycin MICs were 32 to >64 μg/ml, while 17/19 strains had telithromycin MICs of 4 to 16 μg/ml; CEM-101 MICs were 0.015 to 1 μg/ml. By comparison, erm(A) and mef(A) strains had CEM-101 MICs of 0.015 to 0.5 μg/ml, clindamycin and telithromycin MICs of ≤1 μg/ml, and erythromycin, azithromycin, and clarithromycin MICs of 0.5 to >64 μg/ml. Pneumococcal multistep resistance studies showed that although CEM-101 yielded clones with higher MICs for all eight strains tested, seven of eight strains had clones with CEM-101 MICs that rose from 0.004 to 0.03 μg/ml (parental strains) to 0.06 to 0.5 μg/ml (resistant clones); for only one erm(B) mef(A) strain with a parental MIC of 1 μg/ml was there a resistant clone with a MIC of 32 μg/ml, with no detectable mutations in the L4, L22, or 23S rRNA sequence. Among two of five S. pyogenes strains tested, CEM-101 MICs rose from 0.03 to 0.25 μg/ml, and only for the one strain with erm(B) did CEM-101 MICs rise from 1 to 8 μg/ml, with no changes occurring in any macrolide resistance determinant. CEM-101 had low MICs as well as low potential for the selection of resistant mutants, independent of bacterial species or resistance phenotypes in pneumococci and S. pyogenes.

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Antipneumococcal Activity of DK-507k, a New Quinolone, Compared with the Activities of 10 Other Agents

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.47.12.3815-3824.2003 ◽

2003 ◽

Vol 47 (12) ◽

pp. 3815-3824 ◽

Cited By ~ 11

Author(s):

Frederick A. Browne ◽

Bülent Bozdogan ◽

Catherine Clark ◽

Linda M. Kelly ◽

Lois Ednie ◽

...

Keyword(s):

Resistance Mechanisms ◽

Quinolone Resistance ◽

Penicillin G ◽

Agar Dilution ◽

Resistant Strains ◽

Resistant Mutants ◽

Subinhibitory Concentrations ◽

Time Kill

ABSTRACT Agar dilution MIC determination was used to compare the activity of DK-507k with those of ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, sitafloxacin, amoxicillin, cefuroxime, erythromycin, azithromycin, and clarithromycin against 113 penicillin-susceptible, 81 penicillin-intermediate, and 67 penicillin-resistant pneumococci (all quinolone susceptible). DK-507k and sitafloxacin had the lowest MICs of all quinolones against quinolone-susceptible strains (MIC at which 50% of isolates were inhibited [MIC50] and MIC90 of both, 0.06 and 0.125 μg/ml, respectively), followed by moxifloxacin, gatifloxacin, levofloxacin, and ciprofloxacin. MICs of β-lactams and macrolides rose with those of penicillin G. Against 26 quinolone-resistant pneumococci with known resistance mechanisms, DK-507k and sitafloxacin were also the most active quinolones (MICs, 0.125 to 1.0 μg/ml), followed by moxifloxacin, gatifloxacin, levofloxacin, and ciprofloxacin. Mutations in quinolone resistance-determining regions of quinolone-resistant strains were in the usual regions of the parC and gyrA genes. Time-kill testing showed that both DK-507k and sitafloxacin were bactericidal against all 12 quinolone-susceptible and -resistant strains tested at twice the MIC at 24 h. Serial broth passages in subinhibitory concentrations of 10 strains for a minimum of 14 days showed that development of resistant mutants (fourfold or greater increase in the original MIC) occurred most rapidly for ciprofloxacin, followed by moxifloxacin, DK-507k, gatifloxacin, sitafloxacin, and levofloxacin. All parent strains demonstrated a fourfold or greater increase in initial MIC in<50 days. MICs of DK-507k against resistant mutants were lowest, followed by those of sitafloxacin, moxifloxacin, gatifloxacin, ciprofloxacin, and levofloxacin. Four strains were subcultured in subinhibitory concentrations of each drug for 50 days: MICs of DK-507k against resistant mutants were lowest, followed by those of sitafloxacin, moxifloxacin, gatifloxacin, levofloxacin, and ciprofloxacin. Exposure to DK-507k and sitafloxacin resulted in mutations, mostly in gyrA.

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Non-Antibiotics Strategies to Control Salmonella Infection in Poultry

Animals ◽

10.3390/ani12010102 ◽

2022 ◽

Vol 12 (1) ◽

pp. 102

Author(s):

José Martín Ruvalcaba-Gómez ◽

Zuamí Villagrán ◽

Juan José Valdez-Alarcón ◽

Marcelino Martínez-Núñez ◽

Lorena Jacqueline Gomez-Godínez ◽

...

Keyword(s):

Bacterial Infections ◽

Safety Concern ◽

Resistance Mechanisms ◽

Poultry Production ◽

Salmonella Infection ◽

Salmonella Spp ◽

In Ovo ◽

Antimicrobial Substances ◽

Health Significance ◽

Salmonella Control

Salmonella spp. is a facultative intracellular pathogen causing localized or systemic infections, involving economic and public health significance, and remains the leading pathogen of food safety concern worldwide, with poultry being the primary transmission vector. Antibiotics have been the main strategy for Salmonella control for many years, which has allowed producers to improve the growth and health of food-producing animals. However, the utilization of antibiotics has been reconsidered since bacterial pathogens have established and shared a variety of antibiotic resistance mechanisms that can quickly increase within microbial communities. The use of alternatives to antibiotics has been recommended and successfully applied in many countries, leading to the core aim of this review, focused on (1) describing the importance of Salmonella infection in poultry and the effects associated with the use of antibiotics for disease control; (2) discussing the use of feeding-based (prebiotics, probiotics, bacterial subproducts, phytobiotics) and non-feeding-based (bacteriophages, in ovo injection, vaccines) strategies in poultry production for Salmonella control; and (3) exploring the use of complementary strategies, highlighting those based on -omics tools, to assess the effects of using the available antibiotic-free alternatives and their role in lowering dependency on the existing antimicrobial substances to manage bacterial infections in poultry effectively.

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Contribution of Different Mechanisms to Ciprofloxacin Resistance in Salmonella spp.

Frontiers in Microbiology ◽

10.3389/fmicb.2021.663731 ◽

2021 ◽

Vol 12 ◽

Author(s):

Man-Xia Chang ◽

Jin-Fei Zhang ◽

Yin-Huan Sun ◽

Rong-Sheng Li ◽

Xiao-Ling Lin ◽

...

Keyword(s):

Resistance Mechanisms ◽

Quinolone Resistance ◽

Gene Location ◽

Fluoroquinolone Resistance ◽

Salmonella Spp ◽

Resistance Development ◽

Bacterial Fitness ◽

Ciprofloxacin Resistance ◽

Gyra Mutation ◽

Chromosomal Mutations

Development of fluoroquinolone resistance can involve several mechanisms that include chromosomal mutations in genes (gyrAB and parCE) encoding the target bacterial topoisomerase enzymes, increased expression of the AcrAB-TolC efflux system, and acquisition of transmissible quinolone-resistance genes. In this study, 176 Salmonella isolates from animals with a broad range of ciprofloxacin MICs were collected to analyze the contribution of these different mechanisms to different phenotypes. All isolates were classified according to their ciprofloxacin susceptibility pattern into five groups as follows: highly resistant (HR), resistant (R), intermediate (I), reduced susceptibility (RS), and susceptible (S). We found that the ParC T57S substitution was common in strains exhibiting lowest MICs of ciprofloxacin while increased MICs depended on the type of GyrA mutation. The ParC T57S substitution appeared to incur little cost to bacterial fitness on its own. The presence of PMQR genes represented an route for resistance development in the absence of target-site mutations. Switching of the plasmid-mediated quinolone resistance (PMQR) gene location from a plasmid to the chromosome was observed and resulted in decreased ciprofloxacin susceptibility; this also correlated with increased fitness and a stable resistance phenotype. The overexpression of AcrAB-TolC played an important role in isolates with small decreases in susceptibility and expression was upregulated by MarA more often than by RamA. This study increases our understanding of the relative importance of several resistance mechanisms in the development of fluoroquinolone resistance in Salmonella from the food chain.

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Prevalence and characterisation of quinolone resistance mechanisms in Salmonella spp.

Veterinary Microbiology ◽

10.1016/j.vetmic.2014.01.040 ◽

2014 ◽

Vol 171 (3-4) ◽

pp. 307-314 ◽

Cited By ~ 28

Author(s):

Dariusz Wasyl ◽

Andrzej Hoszowski ◽

Magdalena Zając

Keyword(s):

Resistance Mechanisms ◽

Quinolone Resistance ◽

Salmonella Spp

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Dual Targeting of Topoisomerase IV and Gyrase To Reduce Mutant Selection: Direct Testing of the Paradigm by Using WCK-1734, a New Fluoroquinolone, and Ciprofloxacin

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.49.5.1949-1956.2005 ◽

2005 ◽

Vol 49 (5) ◽

pp. 1949-1956 ◽

Cited By ~ 46

Author(s):

Jacob Strahilevitz ◽

David C. Hooper

Keyword(s):

Dna Gyrase ◽

Single Mutation ◽

Topoisomerase Iv ◽

Mutant Selection ◽

Fourfold Increase ◽

Development Of Resistance ◽

Dual Targeting ◽

Gyrase A ◽

Resistant Strains ◽

Selection Of

ABSTRACT Quinolones that act equally against DNA gyrase and topoisomerase IV are a desirable modality to decrease the selection of resistant strains. We first determined by genetic and biochemical studies in Staphylococcus aureus that the primary target enzyme of WCK-1734, a new quinolone, was DNA gyrase. A single mutation in gyrase, but not topoisomerase IV, caused a two- to fourfold increase in the MIC. Studies with purified topoisomerase IV and gyrase from S. aureus also showed that gyrase was more sensitive than topoisomerase IV to WCK-1734 (50% inhibitory concentration, 1.25 and 2.5 to 5.0 μg/ml, respectively; 50% stimulation of cleavage complex formation, 0.62 and 2.5 to 5.0 μg/ml, respectively). To test the effect of balanced activity of quinolones against the two target enzymes, we measured the frequency of selection of mutants with ciprofloxacin (which targets topoisomerase IV) and WCK-1734 alone and in combination. With the combination of ciprofloxacin and WCK-1734, each at its MIC, the ratio of frequency of mutants selected was significantly lower than that with each drug alone at two times their respective MICs. We further characterized resistant strains selected with the combination of ciprofloxacin and WCK-1734 and found evidence to suggest the existence of novel mutational mechanisms for low-level quinolone resistance. By use of a combination of differentially targeting quinolones, this study provides novel data in direct support of the paradigm for dual targeting of quinolone action and reduced development of resistance.

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Spontaneous Quinolone Resistance in the Zoonotic Serovar of Vibrio vulnificus

Applied and Environmental Microbiology ◽

10.1128/aem.02921-08 ◽

2009 ◽

Vol 75 (8) ◽

pp. 2577-2580 ◽

Cited By ~ 9

Author(s):

Francisco J. Roig ◽

A. Llorens ◽

B. Fouz ◽

C. Amaro

Keyword(s):

Vibrio Vulnificus ◽

Quinolone Resistance ◽

Resistant Strains ◽

Selection Of

ABSTRACT This work demonstrates that Vibrio vulnificus biotype 2, serovar E, an eel pathogen able to infect humans, can become resistant to quinolone by specific mutations in gyrA (substitution of isoleucine for serine at position 83) and to some fluoroquinolones by additional mutations in parC (substitution of lysine for serine at position 85). Thus, to avoid the selection of resistant strains that are potentially pathogenic for humans, antibiotics other than quinolones must be used to treat vibriosis on farms.

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Detection of fluoroquinolone resistance by mutation in gyrA gene of Campylobacter spp. isolates from broiler and laying (Gallus gallus domesticus) hens,from Rio de Janeiro State, Brazil

Ciência Rural ◽

10.1590/0103-8478cr20141712 ◽

2015 ◽

Vol 45 (11) ◽

pp. 2013-2018 ◽

Cited By ~ 8

Author(s):

Beatriz da Silva Frasao ◽

Valéria Medeiros ◽

André Victor Barbosa ◽

Waldemir Silva de Aguiar ◽

Felipe Faccini dos Santos ◽

...

Keyword(s):

Direct Sequencing ◽

Fluoroquinolone Resistance ◽

Diffusion Method ◽

Poultry Production ◽

Gyra Gene ◽

Disk Diffusion Method ◽

Resistant Strains ◽

Campylobacter Spp ◽

Selection Of

Poultry are considered to be the main reservoir of Campylobacter spp. bacteria, an important pathogen for humans. Many studies have reported a rapid selection of fluoroquinolone-resistant strains following the widespread use of these antimicrobials in poultry production and human medicine. The main mechanism of fluoroquinolone resistance in Campylobacter is a mutation in the Quinolone Resistance Determinant Region (QRDR) in the gyrA gene, which codes for the subunit of the enzyme DNA gyrase, the target for fluoroquinolone. The aim of this study was to investigate the mutation in QRDR in the gyrA gene of Campylobacter strains previously isolated from broiler carcasses and feces of laying hens. Thirty-eight strains of C. jejuni and 19 C. coli strains (n=57), previously characterized as resistant to ciprofloxacin and enrofloxacin by the disk diffusion method and minimum inhibitory concentration (MIC), were selected. For detection of the mutation, a fragment of 454pb QRDR in the gyrA gene was used for direct sequencing. All strains presented the QRDR mutation in the gyrA gene at codon 86 (Thr-86-Ile), which confers resistance to fluoroquinolones. Other known silent mutations were observed. This genotypic characterization of fluoroquinolone resistance in Campylobacter strains has confirmed the prior phenotypic detection of the resistance. The Thr-86-Ile mutation was observed in all samples confirming that this is the predominant mutation in enrofloxacin and ciprofloxacin resistant strains of C. jejuni and C. coli.

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Phenotypic and molecular characterization of antimicrobial resistance in Proteus mirabilis isolates from dogs

Journal of Medical Microbiology ◽

10.1099/jmm.0.081539-0 ◽

2014 ◽

Vol 63 (11) ◽

pp. 1561-1567 ◽

Cited By ~ 17

Author(s):

Kazuki Harada ◽

Ayaka Niina ◽

Takae Shimizu ◽

Yujiro Mukai ◽

Ken Kuwajima ◽

...

Keyword(s):

Antimicrobial Resistance ◽

Proteus Mirabilis ◽

Large Scale ◽

Antimicrobial Agents ◽

Companion Animals ◽

Resistance Mechanisms ◽

Quinolone Resistance ◽

Class 1 ◽

Resistant Strains

Large-scale monitoring of resistance to 14 antimicrobial agents was performed using 103 Proteus mirabilis strains isolated from dogs in Japan. Resistant strains were analysed to identify their resistance mechanisms. Rates of resistance to chloramphenicol, streptomycin, enrofloxacin, trimethoprim/sulfamethoxazole, kanamycin, ampicillin, ciprofloxacin, cephalothin, gentamicin, cefoxitin and cefotaxime were 20.4, 15.5, 12.6, 10.7, 9.7, 8.7, 5.8, 2.9, 2.9, 1.9 and 1.9 %, respectively. No resistance to ceftazidime, aztreonam or imipenem was found. Class 1 and 2 integrases were detected in 2.9 and 11.7 % of isolates, respectively. Class 1 integrons contained aadB or aadB–catB-like-blaOXA10 –aadA1, whereas those of class 2 contained sat–aadA1, dhfr1–sat–aadA1 or none of the anticipated resistance genes. Of five distinct plasmid-mediated quinolone-resistance (PMQR) genes, only qnrD gene was detected in 1.9 % of isolates. Quinolone-resistance determining regions (QRDRs) of gyrA and parC from 13 enrofloxacin-intermediate and -resistant isolates were sequenced. Seven strains had double mutations and three had single mutations. Three of nine ampicillin-resistant isolates harboured AmpC-type β-lactamases (i.e. bla CMY-2, bla CMY-4 and bla DHA-1). These results suggest that canine Proteus mirabilis deserves continued surveillance as an important reservoir of antimicrobial resistance determinants. This is the first report, to our knowledge, describing integrons, PMQRs and QRDR mutations in Proteus mirabilis isolates from companion animals.

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Antipneumococcal Activity of DW-224a, a New Quinolone, Compared to Those of Eight Other Agents

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00153-06 ◽

2006 ◽

Vol 50 (6) ◽

pp. 2064-2071 ◽

Cited By ~ 11

Author(s):

Klaudia Kosowska-Shick ◽

Kim Credito ◽

Glenn A. Pankuch ◽

Gengrong Lin ◽

Bülent Bozdogan ◽

...

Keyword(s):

Broad Spectrum ◽

Resistance Mechanisms ◽

Quinolone Resistance ◽

Penicillin G ◽

Amoxicillin Clavulanate ◽

Agar Dilution ◽

Efflux Mechanism ◽

Resistant Strains ◽

Azithromycin Resistance

ABSTRACT DW-224a is a new broad-spectrum quinolone with excellent antipneumococcal activity. Agar dilution MIC was used to test the activity of DW-224a compared to those of penicillin, ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, gemifloxacin, amoxicillin-clavulanate, cefuroxime, and azithromycin against 353 quinolone-susceptible pneumococci. The MICs of 29 quinolone-resistant pneumococci with defined quinolone resistance mechanisms against seven quinolones and an efflux mechanism were also tested. DW-224a was the most potent quinolone against quinolone-susceptible pneumococci (MIC50, 0.016 μg/ml; MIC90, 0.03 μg/ml), followed by gemifloxacin, moxifloxacin, gatifloxacin, levofloxacin, and ciprofloxacin. β-Lactam MICs rose with those of penicillin G, and azithromycin resistance was seen mainly in strains with raised penicillin G MICs. Against the 29 quinolone-resistant strains, DW-224a had the lowest MICs (0.06 to 1 μg/ml) compared to those of gemifloxacin, clinafloxacin, moxifloxacin, gatifloxacin, levofloxacin, and ciprofloxacin. DW-224a at 2× MIC was bactericidal after 24 h against eight of nine strains tested. Other quinolones gave similar kill kinetics relative to higher MICs. Serial passages of nine strains in the presence of sub-MIC concentrations of DW-224a, moxifloxacin, levofloxacin, ciprofloxacin, gatifloxacin, gemifloxacin, amoxicillin-clavulanate, cefuroxime, and azithromycin were performed. DW-224a yielded resistant clones similar to moxifloxacin and gemifloxacin but also yielded lower MICs. Azithromycin selected resistant clones in three of the five parents tested. Amoxicillin-clavulanate and cefuroxime did not yield resistant clones after 50 days.

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