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1.
Electron. j. biotechnol ; 41: 9-12, sept. 2019. tab, ilus
Article in English | LILACS | ID: biblio-1053556

ABSTRACT

Background: Horizontal gene transfer (HGT) is the most important mechanism in the evolution of new genetic capabilities in bacteria, including specific degradative pathways, virulence factors, and resistance to antibiotics. Among the processes involved in HGT, transduction is noteworthy. This is a mechanism for gene transmission mediated by a bacteriophage that functions both as a reservoir and as a vector of exogenous genes, which remain protected from environmental effects in the bacteriophage's capsid. Within this context, this investigation aimed to evaluate the ability of the generalized transducing bacteriophage P1 to productively infect and transduce in the bacterial species Salmonella bongori. Results: We could establish that a derivative of bacteriophage P1, P1Cm, infects strains of S. bongori with frequencies of lysogenization in the order of ~10−2 lysogens/UFP. Through thermal induction, infective viral progeny was obtained, and we could show that P1Cm readily formed plaques on S. bongori lawns, a phenomenon thus far not reported for other members of the genus Salmonella. Finally, we showed P1Cm-mediated transduction of the model plasmid RP4 at frequencies of ~10−7 transductants/donor. Conclusion: Therefore, bacteriophage P1 can be used as a tool for the genetic manipulation in the species S. bongori.


Subject(s)
Salmonella , Transduction, Genetic , Bacteriophage P1/genetics , Bacteriophage P1/pathogenicity , Capsid , Gene Transfer, Horizontal , Escherichia coli , Lysogeny
2.
Chinese Journal of Zoonoses ; (12): 105-108,117, 2018.
Article in Chinese | WPRIM | ID: wpr-703076

ABSTRACT

According to CLSI,agar dilution method was used to analyze the minimum inhibitory concentrations (MIC) of the nalidixic acid and ciprofloxacin for the isolates from different sources.Mutations in the quinolone resistant determining region (QRDR) of gyrA and gyrB were examined by DNA sequencing of 102 resistant C.jejuni isolates and 27 sensitive isolates.The results showed that 218 isolates(93.16%) were resistant to nalidixic acid among the entire tested 234 isolates.Among these,the resistant rates of the isolates from chicken feaces,duck feaces,human feaces,food animal and cow feaces were 100.00%,100.00%,97.96%,97.83% and 77.97%,respectively.The 211 isolates(90.17%) were resistant to ciprofloxa-cin.Among these,the resistant rates of the isolates from chicken feaces,duck feaces,human feaces,food animal and cow feaces were 100.00%,100.00%,91.84%,95.65% and 77.97%,respectively.The differences were both statistically significant.All of the resistant isolates on the QRDR of gyrA had Thr-86-Ile mutation.However,the point substitutions in gyrB gene were synonymous mutations.The results indicated that the C.jejuni isolates in this study showed highly resistant to nalidixic acid and ciprofloxacin.The Thr-86-Ile mutation on the QRDR of gyrA can cause highly resistant to quinolone and fluoroquinolone for C.jejuni.

3.
Article in English | IMSEAR | ID: sea-166209

ABSTRACT

In present studies a series of novel 1,8-Naphthyridine derivatives (3a-3f) have been synthesized using nalidixic acid as a starting material. The structures of the compounds were supported by FT-IR, 1H NMR and Mass spectral data. All the synthesized compounds have been evaluated in vitro for their antibacterial activities against several strains of microbes using agar dilution method. The synthesized compounds had moderate to good antibacterial activity. Molecular docking studies reveal that 1,8-Naphthyridine scaffold shared structural complimentary with DNA Gyrase B. Further, TOPKAT analysis on Ames mutagenicity model had shown that this class of compounds have least probability of showing toxicity on experimental animal models.

4.
Article in English | IMSEAR | ID: sea-164445

ABSTRACT

Pseudotumor cerebri is defined as a clinical entity where there are signs and symptoms of raised intracranial pressure but the higher mental and neurological functions are not altered. Many times the etiology is unknown. A thorough history and clinical examination is necessary along with exclusion of possible structural causes of intracranial hypertension. Headache, papilledema and visual disturbances are the characteristic symptoms in a child but in a younger infant it becomes all the more difficult to arrive at diagnose. The prognosis is excellent if the offending drug or cause is identified and abated. This case study reported a case of Pseudotumor cerebri (PTC) in 11 months old child.

5.
Annals of Clinical Microbiology ; : 1-6, 2015.
Article in Korean | WPRIM | ID: wpr-29310

ABSTRACT

BACKGROUND: Most clinical microbiology laboratories in Korea have difficulty in following the recommendations of the clinical procedure handbook for culture of body fluid and wound/abscess specimens. We evaluated the usefulness of MacConkey (MAC) and colistin-nalidixic acid blood agar (CNA) for the isolation of pathogens from these specimens. METHODS: A total of 1,508 clinical specimens [144 peritoneal fluid, 241 body fluids (19 bile, 70 joint fluid, 6 pericardial fluid, 104 pleural fluid, and other fluids in 42 cases) and 1,123 wound/abscess] were inoculated onto basic media [Blood agar plate (BAP), chocolate agar or BAP with streaking of Staphylococcus aureus] and simultaneously inoculated onto MAC and CNA. The pathogens isolated by basic media and by additional use of MAC and/or CNA were compared. RESULTS: With basic media, 885 isolates from 588 specimens were detected, and by additional use of MAC and CNA, an additional 27 isolates from 24 specimens and an additional 128 isolates from 112 specimens were isolated, respectively. Compared to the basic media, by adding MAC, an additional 233.3%, 38.5% and 4.5% of gram-negative bacteria were isolated from peritoneal fluids, body fluid and wound/abscess, respectively, and by adding CNA, an additional 106.7%, 45.0%, and 20.7% of gram-positive bacteria/ yeast were isolated, respectively. The isolates detected by additional use of MAC were mainly Enterobacteriaceae (77.0%), and those detected by CNA were S. aureus (21.1%), Coagulase-negative Staphylococcus spp. (20.3%), Enterococcus spp. (16.4%), Streptococcus spp. (10.2%) and yeasts (16.4%). CONCLUSION: For peritoneal fluid and body fluid specimens, additional use of MAC plus CNA seems necessary for detection of pathogens. For wound/abscess, additional use of CNA will be cost effective.


Subject(s)
Agar , Ascitic Fluid , Bile , Body Fluids , Cacao , Enterobacteriaceae , Enterococcus , Gram-Negative Bacteria , Joints , Korea , Staphylococcus , Streptococcus , Yeasts
6.
Korean Journal of Medicine ; : 340-345, 2015.
Article in Korean | WPRIM | ID: wpr-214125

ABSTRACT

Infection with nontyphoidal Salmonella most often results in self-limited acute gastroenteritis. However, occasionally it causes bacteremia and localized infection requiring antibiotic treatment. A third-generation cephalosporin or fluoroquinolone is often the first choice of antibiotic. However, there has been an increase in nalidixic-acid-resistant nontyphoidal Salmonella with decreased fluoroquinolone susceptibility. Although there have been many cases reported of nontyphoidal Salmonella, no cases of nalidixic-acid-resistant nontyphoidal Salmonella have been reported in Korea. Here, we report on the case of a 61-year-old man with a diagnosis of acute osteomyelitis and periosteal abscess of the femur caused by nalidixic-acid-resistant Salmonella enteritidis. He was treated successfully with prolonged administration of a high-dose of ciprofloxacin and drainage of the abscess.


Subject(s)
Humans , Middle Aged , Abscess , Bacteremia , Ciprofloxacin , Diagnosis , Drainage , Drug Resistance , Femur , Gastroenteritis , Korea , Nalidixic Acid , Osteomyelitis , Salmonella , Salmonella enteritidis
7.
Annals of Clinical Microbiology ; : 50-57, 2014.
Article in Korean | WPRIM | ID: wpr-12610

ABSTRACT

BACKGROUND: Extended-spectrum cephalosporins and fluoroquinolones are important antimicrobials for treating invasive salmonellosis, and emerging resistance to these antimicrobials is of paramount concern. METHODS: A total of 30 Salmonella spp. clinical isolates recovered in Gyeongsangbuk-do from 2012 to 2013 were characterized using antibiotic resistance profiles and pulsed-field gel electrophoresis (PFGE). RESULTS: A high prevalence of multidrug-resistant isolates, mainly showing an ampicillin, nalidixic acid, chloramphenicol resistance pattern, was observed. Four extended-spectrum beta-lactamase (ESBL)-producing isolates (3 CTX-M-15 isolates and 1 CTX-M-27 isolate) were found. The bla(CTX-M-27) gene was carried by an IncF conjugative plasmid in the S. Infantis isolate. The bla(CTX-M-15) gene were carried by an IncF (2 isolates) or IncHI2 (1 isolate) conjugative plasmid in S. Enteritidis. In addition, a single mutation of GyrA, Ser83Thr (1 isolates), Asp87Tyr (9 isolates), Asp87Gly (4 isolates), and Asp87Leu (3 isolates), was detected in nalidixic acid-resistant Salmonella spp. isolates. XbaI PFGE analysis of all isolates revealed more than 19 different pulsotypes. The most common S. Enteritidis PFGE pattern (SEGX01.003) was associated with a larger number of cases of invasive salmonellosis than all other patterns. CONCLUSION: The information from our study can assist in source attribution, outbreak investigations, and tailoring of interventions to maximize disease prevention.


Subject(s)
Ampicillin , beta-Lactamases , Cephalosporins , Chloramphenicol Resistance , Drug Resistance , Drug Resistance, Microbial , Electrophoresis, Gel, Pulsed-Field , Fluoroquinolones , Nalidixic Acid , Plasmids , Prevalence , Salmonella Infections , Salmonella
8.
Korean Journal of Medicine ; : 608-612, 2013.
Article in Korean | WPRIM | ID: wpr-80225

ABSTRACT

Prompt antibiotic treatment reduces the incidence of complications such as liver abscesses, pyelonephritis, and osteomyelitis in patients with typhoid fever. Renal or liver abscesses are especially rare in patients without underlying disease or predisposing factors. The occurrence of both renal and liver abscesses in a patient with typhoid fever has not been reported. Although the prevalence of typhoid fever in Korea has decreased, it is still an important disease owing to increased opportunities for the occurrence of waterborne diseases with climate warming and group feeding, and the increased numbers of tourists and foreigners visiting Korea. We present a patient with no underlying disease or predisposing factors who developed both renal and liver abscesses caused by nalidixic acid-resistant Salmonella typhi after a trip to Nepal. He was treated successfully with percutaneous drainage of the renal abscess and high-dose ciprofloxacin.


Subject(s)
Humans , Abscess , Ciprofloxacin , Climate , Drainage , Drug Resistance , Emigrants and Immigrants , Incidence , Korea , Liver , Liver Abscess , Nalidixic Acid , Nepal , Osteomyelitis , Prevalence , Pyelonephritis , Salmonella , Salmonella typhi , Typhoid Fever
9.
Indian J Med Microbiol ; 2012 Jan-Mar; 30(1): 30-33
Article in English | IMSEAR | ID: sea-143890

ABSTRACT

Purpose: The present study was performed to assess the current susceptibility pattern of blood isolates of Salmonella spp from a super specialty hospital in North India against nalidixic acid, ciprofloxacin and azithromycin and compare the in vitro and in vivo response against azithromycin. Materials and Methods: We evaluated the minimum inhibitory concentration's (MIC's) of 107 blood isolates of Salmonella spp against nalidixic acid, azithromycin and ciprofloxacin and correlated in vitro and in vivo response of azithromycin from the treatment and discharge summaries from the Hospital Information System (HIS) software. Results: Among the 107 isolates evaluated, 94 (87.8%) were nalidixic acid-resistant (NAR) Salmonella and 36 were resistant to azithromycin by MIC testing. The MIC 90 value for azithromycin was 24 μg/mL. Among the 57 treatment histories evaluated using the HIS software, 19 (33%) patients had documented clinical non-response to azithromycin which required change of therapy. Conclusions: The present study observed a higher MIC 90 values for azithromycin compared to Salmonella isolates from Western studies. There was also a documented clinical non-response against azithromycin. The in vitro and in vivo findings in this study suggest a guarded use of azithromycin for cases of enteric fever in India. The study also augments the reversal of resistance pattern in favour of chloramphenicol, ampicillin and trimethoprim - sulfamethoxazole.


Subject(s)
Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Azithromycin/pharmacology , Azithromycin/therapeutic use , Ciprofloxacin/pharmacology , Ciprofloxacin/therapeutic use , Humans , India , Microbial Sensitivity Tests , Nalidixic Acid/pharmacology , Nalidixic Acid/therapeutic use , Salmonella typhi/drug effects , Salmonella typhi/isolation & purification , Typhoid Fever/drug therapy , Typhoid Fever/microbiology
10.
Journal of Bacteriology and Virology ; : 203-210, 2012.
Article in English | WPRIM | ID: wpr-200177

ABSTRACT

A total of 91 non-typhoid Salmonella isolated from pediatric patients with diarrhea in Seoul from 2003 to 2009 was tested for antimicrobial susceptibility of nalidixic acid (NA). Forty strains of NA resistance or intermediate susceptible non-typhoid Salmonella were identified and their minimum inhibitory concentrations (MICs) of NA, ciprofloxacin (CIP), and norfloxacin (NOR) were determined. Of the 40 isolates, 26 were resistant to NA (MIC >256 microg/ml). Only one isolate was high-level resistant to CIP (12 microg/ml) and NOR (48 microg/ml). Mutations in gyrA and parC genes were studied by PCR and sequencing. All NA-resistant isolates carried point mutations in the gyrA quinolone resistance determining regions (QRDR) at codon 83 or 87 (MICs of NA, >256 microg/ml; MICs of CIP, 0.047~0.25 microg/ml; MICs of NOR, 0.38~1.5 microg/ml). A double change in GyrA was found in one Salmonella Enteritidis (MIC of CIP, 12 microg/ml; MIC of NOR, 48 microg/ml). In respect of the ParC protein, a single change at Thr57-->Ser was found in 3 isolates (MICs of NA, >256 microg/ml; MICs of CIP, 0.19~0.25 microg/ml; MICs of NOR, 1 microg/ml). At the same time, these strains changed from Ser83 to Tyr in the gyrA. The result of the investigation for the prevalence of plasmid-mediated quinolone resistance (PMQR) genes, 14 isolates harbored qnr gene among 40 isolates. All of 14 isolates showed decreased susceptibility at NA (MICs 4~16 microg/ml) and except one strain, all of qnr genes were identified as qnrB. Mutations in the gyrA gene and production of PMQR determinants were critical for quinolone resistance and decreased susceptibility to fluoroquinolone in these isolates.


Subject(s)
Humans , Ciprofloxacin , Codon , Diarrhea , DNA Topoisomerase IV , Microbial Sensitivity Tests , Nalidixic Acid , Norfloxacin , Point Mutation , Polymerase Chain Reaction , Prevalence , Salmonella , Salmonella enteritidis , Sprains and Strains
11.
Article in English | IMSEAR | ID: sea-150894

ABSTRACT

Blood-stream pathogens were investigated between 2005 and 2009 in 262 patients with septicaemia in Maiduguri Metropolis, Nigeria to evaluate trends in fluoroquinolones activities against them. Blood samples were cultured in an enriched nutrient agar while susceptibilities tests were performed using the disc diffusion techniques.Staphylococcus aureus, the predominant pathogen accounted for 57.6% and peaking in 2007 with 26.5%. Salmonella spp (overall: 20.2%) infectivity increased from 2006-2008 by 15% but Klebsiella bacteraemia (14.9%) decreased by 20.7% from 2006-2008. Bacteraemia caused by Escherichia coli (7.3%) was the least. The S. aureus sensitivity to ciprofloxacin decreased by 25% between 2005 and 2007 while ofloxacin steady decrease from 2005 to 2008 by 33% showed significant correlation (P<0.05). Ciprofloxacin activities against norfloxacin-resistant and pefloxacin-resistant S. aureus (74.5% and 75% respectively) are both significantly different (P<0.005) from ofloxacin (27.7% and 37.5% respectively) but 92%, 81% and 78% of nalidixic acid-resistant Klebsiella spp are sensitive to ciprofloxacin, ofloxacin and pefloxacin respectively. The ofloxacin’s activities against E. coli were superior to ciprofloxacin with 50%, 69% and 94% of nalidixic acid-resistant E. coli being sensitive to pefloxacin, ciprofloxacin and ofloxacin respectively. However all ciprofloxacin-resistant E. coli are ofloxacin-sensitive. The study found occurrence of continuous and significant loss in activities of most fluoroquinolones against S. aureus and E. coli but while ciprofloxacin indicated high activities against S. aureus and Klebsiella bacteraemia, ofloxacin was superior against E. coli and Salmonella bacteaemia than other agents.

13.
Chinese Journal of Laboratory Medicine ; (12): 431-436, 2011.
Article in Chinese | WPRIM | ID: wpr-417243

ABSTRACT

Objective To investigate the antimicrobial resistance mechanisms and genetic homogeny of Salmonella from community acquired infections in Shenzhen,China.Methods Ninety-three of Salmonella were isolated from 2002 to 2007 at Shenzhen People's Hospital,China.PCR and DNA sequencing were used to investigate the mutation in QRDR of the gyrA,gyrB,parC and parE.Plasmid mediated quinolone resistance genes including qnr and aac(6')-Ib-cr,β-lactamase genes including blaTEM,blaSHV,blaOXA, blaCTX-M, and class 1 integron were detected. All isolates were typed by PFGE. Results S. enterica typhi and S. enterica paratyphi A were susceptible to ampicillin, chloramphenicol, trimethoprim/sulfamethoxazole, ceftriaxone and ciprofloxacin, with the susceptible rate of 96%-100%. Fifty-two percent (13/25) of S. enterica typhi and 95% (61/64) of S. enterica paratyphi A were resistant to nalidixic acid. Twenty-four percent (6/25) of nalidixic acid-resistant S. enterica typhi and 94% (60/64) of nalidixic acid-resistant S. enterica paratyphi A showed decreased susceptibility to ciprofloxacin (MIC of 0. 125-1 μg/ml).All nalidixic acid-resistant (susceptible to ciprofloxacin ) Salmonella (NARS) isolates had a single substitution in the QRDR of GyrA, and 91% (68/75) of these isolates carried the substitution Ser83Phe in GyrA. Two mutations in the QRDR of GyrA were detected in both of two ciprnfloxacin-resistant Salmonella,with the additional one mutation in the QRDR of parC. Plasmid mediated quinolone resistance genes including qnr and aac(6')-lb-cr were not detected in any isolate. The blaCTX-M-14 gene was detected in a ceftriaxoneresistant isolate of S. enterica paratyphi A, with ISEcpl located on the upstream of it. Three muhidrugresistant strains of Salmonella all carried one 1 900 bp classⅠ integron gene cassette dhfrⅫ-orfF-aadA2,with the additional one β-lactamase gene of blaTEM-1, or blaOXA-30. Twenty-two distinct PFGE patterns were observed among twenty-five S. enterica typhi. The PFGE patterns of sixty-four S. enterica paratyphi A showed limited genetic diversity (average similarity of 91% ). Ninety investigated inpatients were infected in the community. Six patients infected by S. enterica paratyphi A had a travel history before infection. Conclusions Nalidixic acid-resistant S. enterica typhi and S. enterica paratyphi A are highly prevalent in Shenzhen,China. The mutation in the QRDR of GyrA is the prevalent mechanism responsible for the resistance to nalidixic acid in Slmonella. The great genetic similarity among S. enterica paratyphi A isolates indicates endemic disease from the presence of a single clone over 6-year period.

14.
Indian J Med Microbiol ; 2010 Jan-Mar; 28(1): 51-53
Article in English | IMSEAR | ID: sea-143647

ABSTRACT

This retrospective study incorporates a six years, six months (January 2000-June 2006) laboratory data comprising 258 isolates of Salmonella. Cultures were identified by standard methods. Salmonella enterica serotype Typhi (S.Typhi) was the more frequent serotype isolated i.e., 61.62% with the remaining 38.37% being Salmonella enterica serotype Paratyphi A (S. Paratyphi A). There was emergence of S. Paratyphi A as the predominant serotype in 2003-2004 with resurgence of serotype Typhi thereon. A total of 66.27% isolates were resistant to one or more antibiotics. MDR S. Typhi was 10.69% and while 13.13% were MDR S. Paratyphi A. There was decrease in resistance to ampicillin, cotrimoxazole in 2004 and nalidixic acid beyond 2005 and increase in resistance to cefuroxime. We also documented a decrease in resistance to ciprofloxacin after 2005.

15.
Infection and Chemotherapy ; : 230-236, 2010.
Article in English | WPRIM | ID: wpr-96935

ABSTRACT

BACKGROUND: Non-typhoidal Salmonella (NTS) are important commensal microorganisms. We intended to investigate the prevalence and mechanisms of nalidixic acid resistance among NTS isolated from human and poultry/livestock. METHODS: A total of 151 Salmonella isolates (36 human and 115 livestock isolates, respectively) was tested for the Minimum inhibitory concentrations (MICs) of nalidixic acid, together with serotyping. As for the nalidixic acid resistant isolates, further studies were taken: MICs of ciprofloxacin, mutation analysis of gyrA and parC genes, and organic solvent tolerance test. RESULTS: Eighty-four isolates of 151 human and livestock isolates were resistant to nalidixic acid. The prevalence of nalidixic acid resistance and was 13.9% (5 of 36 isolates) in human isolates and 68.7% (79 of 151 isolates), in the livestock isolates respectively. Among 84 nalidixic acid-resistant isolates, the The prevalence of ciprofloxacin resistance in livestock isolates was 24.1% (1 resistant and 18 intermediate of 79 strains), but no ciprofloxacin resistance was found in 5 human isolates. Among 65 nalidixic acid resistant, ciprofloxacin-susceptible isolates, 3 (60%, of 5 human isolates) and 60 (100%, all livestock isolates) showed low level fluoroquinolone resistance (ciprofloxacin MIC, 0.125-1.0 microgram/microliter). Six types of point mutations were found in the analysis of DNA sequencing of the gyrA gene in the 84 isolates; 75 isolates showed point mutations on amino acid Ser 83 and/or Asp 87. On the other hand, no point mutation was found from the parC genes. Forty-seven nalidixic acid resistant isolates showed tolerance to organic solvents. CONCLUSIONS: Nalidixic acid resistance was a good marker of low level fluoroquinolone resistance. As for the severe NTS infection, MIC test for nalidixic acid would be required.


Subject(s)
Humans , Ciprofloxacin , Hand , Livestock , Microbial Sensitivity Tests , Nalidixic Acid , Point Mutation , Prevalence , Salmonella , Sequence Analysis, DNA , Serotyping , Solvents , Viperidae
16.
Indian J Pathol Microbiol ; 2009 Oct-Dec; 52(4): 505-508
Article in English | IMSEAR | ID: sea-141536

ABSTRACT

Background and Objectives: Chloramphenicol was considered the anti-microbial gold standard for typhoid treatment but, following the increasing worldwide frequency of antibiotic resistance, ciprofloxacin has been the mainstay of therapy since 1980. Recent studies have shown a shifting of susceptibility to conventional drugs like chloramphenicol, ampicillin and cotrimoxazole. The primary objective of the study was to evaluate the in vitro activity of chloramphenicol and other first-line drugs in comparison with cephalosporins and quinolones. Materials and Methods: Fifty isolates of Salmonella obtained from blood culture were subjected to serotyping at the Central Research Institute, Kasauli. Phage typing and biotyping was performed at the National Phage Typing Centre, New Delhi. Antibiotic sensitivity testing was carried out for 10 drugs by the Kirby-Bauer disc diffusion method and minimum inhibitory concentration by broth microdilution for nalidixic acid, chloramphenicol, ciprofloxacin, ceftriaxone, cefixime and ofloxacin. Multi-drug-resistant (MDR) strains were checked for plasmid. Results: In the present study, 70 and 30% of the isolates were Salmonella enterica serovar typhi and paratyphi A, respectively. They were highly sensitive to chloramphenicol (86%), ampicillin (84%) and cotrimoxazole (88%). Highest sensitivity was seen for cephalosporins, followed by quinolones. Seventeen/21 (81%) and 100% of the Salmonella enterica serovar typhi strains belonged to E1 phage type and biotype 1, respectively. Antibiogram showed 2% of the strains to be sensitive to all the drugs tested and 12% were MDR and showed the presence of plasmids. Conclusion: The study indicates reemergence of chloramphenicol-susceptible Salmonella enterica serovar typhi and paratyphi A isolates, a significant decline in MDR strains and high resistance to nalidixic acid. E1 phage type and biotype 1 are found to be most prevalent in Chennai, India.

17.
Indian J Biochem Biophys ; 2009 Apr; 46(2): 147-153
Article in English | IMSEAR | ID: sea-135187

ABSTRACT

The quinolones exert their anti-bacterial activity by binding to DNA gyrase A (GyrA), an essential enzyme in maintenance of DNA topology within bacterial cell. The mutations conferring resistance to quinolones arise within the quinolone-resistance-determining region (QRDR) of GyrA. Therefore, quinolones interaction with wild and mutated GyrA can provide the molecular explanation for resistance. Resistant strains of Salmonella enterica of our hospital have shown mutations in the QRDR of GyrA of serine 83 (to phenylalanine or tyrosine) or aspartic acid 87 (to glycine or tyrosine). In order to understand the association between observed resistance and structural alterations of GyrA with respect to quinolone binding, we have studied the interaction of mutated QRDR of GyrA with nalidixic acid and ciprofloxacin by molecular modeling using GLIDE v4. Analysis of interaction parameters like G-score has revealed reduced interaction between nalidixic acid/ciprofloxacin with QRDR of GyrA in all four mutated cases of resistant strains. The mutation of Ser83 to Phe or Tyr shows least binding for nalidixic acid, while Asp87 to Gly or Tyr exhibits minimal binding for ciprofloxacin. The study also highlights the important role of arginines at 21, 91 and His at 45, which form strong hydrogen bonds (at < 3 Å) with quinolones. The hydrophilic OH group of Serine 83, which is in close proximity to the quinolone binding site is replaced by aromatic moieties of Tyr or Phe in mutated GyrA. This replacement leads to steric hindrance for quinolone binding. Therefore, quinolone resistance developed by Salmonella appears to be due to the decreased selectivity and affinity of nalidixic acid/ciprofloxacin to QRDR of GyrA.


Subject(s)
Amino Acid Sequence , Ciprofloxacin/chemistry , Ciprofloxacin/metabolism , DNA Gyrase/chemistry , DNA Gyrase/genetics , DNA Gyrase/metabolism , Drug Resistance, Bacterial/genetics , Models, Molecular , Molecular Conformation , Molecular Sequence Data , Mutant Proteins/chemistry , Mutant Proteins/genetics , Mutant Proteins/metabolism , Mutation , Nalidixic Acid/chemistry , Nalidixic Acid/metabolism , Protein Binding
18.
Chinese Journal of Nosocomiology ; (24)2009.
Article in Chinese | WPRIM | ID: wpr-596435

ABSTRACT

OBJECTIVE To explore the gene gyrA mutation in nalidixic acid-resistant Salmonella paratyphi A(SPA) in Shaoxing area.METHODS Fifty-two strains of SPA gene were assessed by amplification and purification and the PCR products were detected by two directional sequencing methods.The sequences of DNA gyrase A were compared and analyzed with the OMIGA2.0 software,and the gene gyrA mutation was identified.RESULTS The mutation in nalidixic acid-resistant SPA was discovered in No.83 or No.87 animo acid site of gyrA quinolones resistant determinate region(QRDR),and the mutation of 51 strains occurred in No.83 site,1 strain occurred in No.87 site.The simultaneous mutation of two sites was not discovered,No mutations were found in other sites of gyrA QRDR.CONCLUSIONS No.83 site mutations of gene gyrA has a direct relation to nalidixic acid-resistant SPA.No.87 site mutation of gene gyrA might also cause nalidixic acid-resistantce.The nalidixic acid-resistant SPA is mainly mutated in No.83 site by TCC→TTC(Ser→Phe) in Shaoxing area.

19.
Korean Journal of Medicine ; : 371-375, 2009.
Article in Korean | WPRIM | ID: wpr-150699

ABSTRACT

Kaposi sarcoma in acquired immunodeficiency syndrome (AIDS) is rarely seen in Korea and the incidence has declined in the era of highly active antiretroviral therapy (HAART). Visceral involvement in patients having AIDS with Kaposi sarcoma is more common than in patients infected with non-human immunodeficiency virus. Visceral involvement may be asymptomatic and usuallydoes not require specific therapy. Chemotherapy is usually used in symptomatic or rapidly progressive disease, and interferon- alpha can be applied as an alternative treatment option. Compared to cutaneous Kaposi sarcoma in AIDS, only three cases of gastrointestinal Kaposi sarcoma in patients with AIDS have been reported in Korea, and no experience with interferon therapy for AIDS-associated visceral Kaposi sarcoma has been reported. We report a case of gastrointestinal Kaposi sarcoma in a patient with AIDS who had combined treatment with interferon-alpha and HAART.


Subject(s)
Humans , Acquired Immunodeficiency Syndrome , Antiretroviral Therapy, Highly Active , Ciprofloxacin , Drug Resistance , Incidence , Interferon-alpha , Interferons , Korea , Nalidixic Acid , Sarcoma, Kaposi , Typhoid Fever , Viruses
20.
Korean Journal of Medicine ; : 377-381, 2009.
Article in Korean | WPRIM | ID: wpr-150698

ABSTRACT

Recently, the role of ciprofloxacin in the empirical treatment of typhoid fever has been limited with the increased incidence of nalidixic acid-resistant Salmonella enterica serovar Typhi in South-central and Southeast Asia, as well as multidrug-resistant strains. We experienced three cases of imported typhoid fever that did not respond to ciprofloxacin. All of the blood isolates were susceptible to ciprofloxacin in vitro, but the patients failed to achieve clinical improvement with ciprofloxacin and were treated with ceftriaxone or azithromycin. Although nalidixic acid-resistant strains may be reported as susceptible to ciprofloxacin on disk diffusion tests, they frequently show a poor clinical response to ciprofloxacin because of the increased minimum inhibitory concentration of ciprofloxacin. Therefore, if clinical improvement is delayed or fails with ciprofloxacin, imported typhoid fever from South-central or Southeast Asia should be considered as being due to nalidixic acid-resistant strains and should be treated with high-dose ciprofloxacin, ceftriaxone, or azithromycin.


Subject(s)
Humans , Asia, Southeastern , Azithromycin , Ceftriaxone , Ciprofloxacin , Diffusion , Drug Resistance , Incidence , Microbial Sensitivity Tests , Nalidixic Acid , Salmonella typhi , Treatment Failure , Typhoid Fever
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