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1.
Ghana Med J ; 58(1): 86-90, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38957275

RESUMO

Objective: This study aims to examine the frequency of Salmonella Paratyphi found in blood cultures and evaluate the antibiotic susceptibility pattern of Salmonella isolates to different antibiotics. Additionally, the study aims to assess the paradigm shift in the trend of enteric fever caused by Salmonella Typhi (S. Typhi) to Salmonella Paratyphi(S. Paratyphi) . Study Design: Retrospective study. Participant: The study enrolled patients aged 12 years and above diagnosed with enteric fever (positive blood culture) and admitted to Peelamedu Samanaidu Govindasamy Naidu (PSG) Hospital. Interventions: The study analyzed demographic and antibiotic susceptibility profiles of Salmonella isolates collected from 106 enteric fever patients in the hospital between 2010 and 2022. The susceptibility profiles of Salmonella isolates to multiple antibiotics were assessed. Results: There were 106 participants, and 95 (89.62%) of them had enteric fever linked to Salmonella Typhi, while only 11 (10.38%) had enteric fever linked to Salmonella Paratyphi A. From 2010 to 2022, the study discovered a general decline in the prevalence of enteric fever caused by Salmonella species. But between 2014 and 2022, the incidence of enteric fever linked to S. Typhi rapidly increased. Azithromycin (100% , n = 106) and ceftriaxone (99% , n = 105) were highly effective against the Salmonella isolates, whereas nalidixic acid was resisted by 3 isolates (4.72%, n = 3). Conclusion: The study observed a higher incidence of Salmonella Typhi in comparison to Paratyphi A and a greater susceptibility of males to enteric fever. Funding: None declared.


Assuntos
Antibacterianos , Testes de Sensibilidade Microbiana , Salmonella paratyphi A , Salmonella typhi , Febre Tifoide , Humanos , Masculino , Feminino , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Febre Tifoide/epidemiologia , Febre Tifoide/microbiologia , Febre Tifoide/tratamento farmacológico , Estudos Retrospectivos , Salmonella typhi/efeitos dos fármacos , Salmonella typhi/isolamento & purificação , Salmonella paratyphi A/efeitos dos fármacos , Salmonella paratyphi A/isolamento & purificação , Adulto , Adolescente , Criança , Pessoa de Meia-Idade , Adulto Jovem , Febre Paratifoide/epidemiologia , Febre Paratifoide/microbiologia , Febre Paratifoide/tratamento farmacológico , Incidência , Farmacorresistência Bacteriana , Azitromicina/uso terapêutico , Azitromicina/farmacologia , Ceftriaxona/uso terapêutico , Ceftriaxona/farmacologia , Idoso , Prevalência
2.
Commun Biol ; 7(1): 775, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38942806

RESUMO

Antimicrobial resistance (AMR) poses a serious threat to the clinical management of typhoid fever. AMR in Salmonella Typhi (S. Typhi) is commonly associated with the H58 lineage, a lineage that arose comparatively recently before becoming globally disseminated. To better understand when and how H58 emerged and became dominant, we performed detailed phylogenetic analyses on contemporary genome sequences from S. Typhi isolated in the period spanning the emergence. Our dataset, which contains the earliest described H58 S. Typhi organism, indicates that ancestral H58 organisms were already multi-drug resistant (MDR). These organisms emerged spontaneously in India in 1987 and became radially distributed throughout South Asia and then globally in the ensuing years. These early organisms were associated with a single long branch, possessing mutations associated with increased bile tolerance, suggesting that the first H58 organism was generated during chronic carriage. The subsequent use of fluoroquinolones led to several independent mutations in gyrA. The ability of H58 to acquire and maintain AMR genes continues to pose a threat, as extensively drug-resistant (XDR; MDR plus resistance to ciprofloxacin and third generation cephalosporins) variants, have emerged recently in this lineage. Understanding where and how H58 S. Typhi originated and became successful is key to understand how AMR drives successful lineages of bacterial pathogens. Additionally, these data can inform optimal targeting of typhoid conjugate vaccines (TCVs) for reducing the potential for emergence and the impact of new drug-resistant variants. Emphasis should also be placed upon the prospective identification and treatment of chronic carriers to prevent the emergence of new drug resistant variants with the ability to spread efficiently.


Assuntos
Antibacterianos , Filogenia , Salmonella typhi , Febre Tifoide , Salmonella typhi/genética , Salmonella typhi/efeitos dos fármacos , Febre Tifoide/microbiologia , Febre Tifoide/tratamento farmacológico , Febre Tifoide/epidemiologia , Humanos , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Haplótipos , Mutação , Genoma Bacteriano
3.
PLoS One ; 19(6): e0303285, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38917154

RESUMO

Typhoid fever, caused by Salmonella enterica serovar typhi, presents a substantial global health threat, particularly in regions with limited healthcare infrastructure. The rise of multidrug-resistant strains of S. typhi exacerbates this challenge, severely compromising conventional treatment efficacy due to over activity of efflux pumps. In our study, a comprehensive exploration of two fundamental aspects to combat MDR in S. typhi is carried out; i.e. employing advanced bioinformatics analyses and AlphaFold AI, We successfully identified and characterised a putative homologue, ABC-TPA, reminiscent of the P-glycoprotein (P-gp) known for its role in multidrug resistance in diverse pathogens. This discovery provides a critical foundation for understanding the potential mechanisms driving antibiotic resistance in S. typhi. Furthermore, employing computational methodologies, We meticulously assessed the potential of lignans, specifically Schisandrin A, B, and C, as promising Efflux Pump Inhibitors (EPIs) against the identified P-gp homologue in S. typhi. Noteworthy findings revealed robust binding interactions of Schisandrin A and B with the target protein, indicating substantial inhibitory capabilities. In contrast, Schisandrin C exhibited instability, showing varied effectiveness among the evaluated lignans. Pharmacokinetics and toxicity predictions underscored the favourable attributes of Schisandrin A, including prolonged action duration. Furthermore, high systemic stability and demanished toxicity profile of SA and SB present their therapeutic efficacy against MDR. This comprehensive investigation not only elucidates potential therapeutic strategies against MDR strains of S. typhi but also highlights the relevance of computational approaches in identifying and evaluating promising candidates. These findings lay a robust foundation for future empirical studies to address the formidable challenges antibiotic resistance poses in this clinically significant infectious diseases.


Assuntos
Antibacterianos , Farmacorresistência Bacteriana Múltipla , Lignanas , Salmonella typhi , Salmonella typhi/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Lignanas/farmacologia , Lignanas/química , Antibacterianos/farmacologia , Antibacterianos/química , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/genética , Humanos , Testes de Sensibilidade Microbiana , Biologia Computacional/métodos
4.
J Pediatric Infect Dis Soc ; 13(6): 337-339, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38717105

RESUMO

Extensively drug-resistant (XDR) strains of Salmonella enterica serotype Typhi have emerged in Pakistan and Iraq. We report 13 children with enteric fever in Southeast Texas seen over 3.5 years, of whom 23.1% had XDR isolates.


Assuntos
Salmonella typhi , Febre Tifoide , Humanos , Texas/epidemiologia , Febre Tifoide/epidemiologia , Febre Tifoide/tratamento farmacológico , Febre Tifoide/microbiologia , Pré-Escolar , Criança , Masculino , Feminino , Salmonella typhi/efeitos dos fármacos , Salmonella typhi/isolamento & purificação , Antibacterianos/uso terapêutico , Lactente , Farmacorresistência Bacteriana Múltipla , Adolescente
5.
ACS Infect Dis ; 10(6): 1990-2001, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38815059

RESUMO

Conserved molecular signatures in multidrug-resistant Salmonella typhi can serve as novel therapeutic targets for mitigation of infection. In this regard, we present the S. typhi cell division activator protein (StCAP) as a conserved target across S. typhi variants. From in silico and fluorimetric assessments, we found that StCAP is a DNA-binding protein. Replacement of the identified DNA-interacting residue Arg34 of StCAP with Ala34 showed a dramatic (15-fold) increase in Kd value compared to the wild type (Kd 546 nm) as well as a decrease in thermal stability (10 °C shift). Out of the two screened molecules against the DNA-binding pocket of StCAP, eltrombopag, and nilotinib, the former displayed better binding. Eltrombopag inhibited the stand-alone S. typhi culture with an IC50 of 38 µM. The effect was much more pronounced on THP-1-derived macrophages (T1Mac) infected with S. typhi where colony formation was severely hindered with IC50 reduced further to 10 µM. Apoptotic protease activating factor1 (Apaf1), a key molecule for intrinsic apoptosis, was identified as an StCAP-interacting partner by pull-down assay against T1Mac. Further, StCAP-transfected T1Mac showed a significant increase in LC3 II (autophagy marker) expression and downregulation of caspase 3 protein. From these experiments, we conclude that StCAP provides a crucial survival advantage to S. typhi during infection, thereby making it a potent alternative therapeutic target.


Assuntos
Proteínas de Bactérias , Salmonella typhi , Salmonella typhi/efeitos dos fármacos , Salmonella typhi/genética , Salmonella typhi/patogenicidade , Humanos , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Apoptose/efeitos dos fármacos , Macrófagos/microbiologia , Macrófagos/efeitos dos fármacos , Células THP-1 , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Autofagia/efeitos dos fármacos , Febre Tifoide/microbiologia , Divisão Celular/efeitos dos fármacos
6.
Diagn Microbiol Infect Dis ; 109(4): 116354, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38776664

RESUMO

The study was done to assess the antimicrobial susceptibility pattern among Salmonella enterica serovars causing bacteremia in Northern India. In this observational study, blood samples positive for Salmonella enterica serovars from January 2021 to April 2023 were studied. Species identification was done using MALDI-ToF MS. Serotyping was done using slide agglutination method. Antimicrobial susceptibility was interpreted as per the CLSI guidelines. During the study period, 32 Salmonella enterica serovars were isolated. Salmonella enterica serovar Typhi was the predominant serovar, followed by Salmonella enterica serovar Paratyphi A. All isolates were susceptible to ceftriaxone, chloramphenicol, co-trimoxazole and cefotaxime. Pefloxacin showed 100% resistance. Resistance to nalidixic acid was found in 81.2% isolates. Of the isolates resistant to nalidixic acid, 19(73.08%) isolates were resistant to ciprofloxacin also. This changing susceptibility pattern necessitates continuous surveillance of antibiogram of Salmonella isolates to rationalize the treatment protocols for invasive salmonellosis and prevent emergence of resistant strains.


Assuntos
Antibacterianos , Bacteriemia , Testes de Sensibilidade Microbiana , Infecções por Salmonella , Centros de Atenção Terciária , Humanos , Bacteriemia/microbiologia , Bacteriemia/epidemiologia , Índia/epidemiologia , Centros de Atenção Terciária/estatística & dados numéricos , Antibacterianos/farmacologia , Infecções por Salmonella/microbiologia , Infecções por Salmonella/epidemiologia , Sorogrupo , Salmonella enterica/efeitos dos fármacos , Salmonella enterica/isolamento & purificação , Salmonella/efeitos dos fármacos , Salmonella/isolamento & purificação , Salmonella/classificação , Adulto , Masculino , Farmacorresistência Bacteriana , Sorotipagem , Pessoa de Meia-Idade , Adulto Jovem , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Feminino , Salmonella typhi/efeitos dos fármacos , Salmonella typhi/isolamento & purificação
7.
J Infect Dev Ctries ; 18(4): 550-555, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38728649

RESUMO

INTRODUCTION: Pakistan has been experiencing an extensively drug-resistant (XDR) outbreak of typhoid for some years. We sought to evaluate how the COVID-19 pandemic impacted typhoid epidemiology in Pakistan, from the beginning of the pandemic in 2020 through the end of 2022, and the reduction of COVID-19 cases. METHODOLOGY: We compared national public COVID-19 data with retrospectively obtained patient data of confirmed S. Typhi isolates between January 2019 and December 2022 from Shaukat Khanum Memorial Cancer Hospital and Research Centre and the hospital's extended network of laboratory collection centers across Pakistan. RESULTS: We observed that during the early onset of the COVID-19 pandemic and COVID-19 peaks, typhoid positivity generally decreased. This suggests that restrictions and non-pharmaceutical interventions that limited social interactions and promoted good sanitation and hygiene practices had a positive secondary effect on typhoid. This led to an overall yearly decrease in typhoid positivity between 2019 to 2021. However, the percentage of S. Typhi cases isolated that were ceftriaxone-resistant continued to increase, suggesting the continued dominance of XDR typhoid in Pakistan. In 2022, with the alleviation of pandemic restrictions, we observed increased typhoid positivity and COVID-19 and typhoid positivity started to follow similar trends. CONCLUSIONS: Given the continued presence of COVID-19 along with XDR typhoid in Pakistan, it will be imperative to use differential testing to ensure that the epidemiology of each reported is accurate, the spread of each it contained, and that antibiotics are not misused. The use of approved vaccinations will lessen the burden of both diseases.


Assuntos
COVID-19 , Salmonella typhi , Febre Tifoide , Febre Tifoide/epidemiologia , Paquistão/epidemiologia , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Salmonella typhi/efeitos dos fármacos , Salmonella typhi/isolamento & purificação , Estudos Retrospectivos , SARS-CoV-2 , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia
8.
Microb Pathog ; 191: 106676, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38710290

RESUMO

Enteric fever, a persistent public health challenge in developing regions, is exacerbated by suboptimal socioeconomic conditions, contaminated water and food sources, and insufficient sanitation. This study delves into the antimicrobial susceptibility of Salmonella Typhi, uncovering the genetic underpinnings of its resistance. Analyzing 897 suspected cases, we identified a significant prevalence of typhoid fever, predominantly in males (58.3 %) and younger demographics. Alarmingly, our data reveals an escalation in resistance to both primary and secondary antibiotics, with cases of multi-drug resistant (MDR) and extensively drug-resistant (XDR) S. Typhi reaching 14.7 % and 43.4 %, respectively, in 2021. The Multiple Antibiotic Resistance (MAR) index exceeded 0.2 in over half of the isolates, signaling widespread antibiotic misuse. The study discerned 47 unique antibiotic resistance patterns and pinpointed carbapenem and macrolide antibiotics as the remaining effective treatments against XDR strains, underlining the critical need to preserve these drugs for severe cases. Molecular examinations identified blaTEM, blaSHV, and blaCTX-M genes in ceftriaxone-resistant strains, while qnrS was specific to ciprofloxacin-resistant variants. Notably, all examined strains exhibited a singular mutation in the gyrA gene, maintaining wild-type gyrB and parC genes. The erm(B) gene emerged as the primary determinant of azithromycin resistance. Furthermore, a distressing increase in resistance genes was observed over three years, with erm(B), blaTEM and qnrS showing significant upward trends. These findings are a clarion call for robust antimicrobial stewardship programs to curtail inappropriate antibiotic use and forestall the burgeoning threat of antibiotic resistance in S. Typhi.


Assuntos
Antibacterianos , Farmacorresistência Bacteriana Múltipla , Testes de Sensibilidade Microbiana , Salmonella typhi , Febre Tifoide , Febre Tifoide/microbiologia , Febre Tifoide/epidemiologia , Salmonella typhi/efeitos dos fármacos , Salmonella typhi/genética , Humanos , Antibacterianos/farmacologia , Masculino , Feminino , Farmacorresistência Bacteriana Múltipla/genética , Adulto , Pré-Escolar , Adolescente , Criança , Adulto Jovem , Pessoa de Meia-Idade , Lactente , Prevalência , Idoso , Farmacorresistência Bacteriana/genética , Mutação , Proteínas de Bactérias/genética
9.
J Paediatr Child Health ; 60(6): 188-192, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38661078

RESUMO

BACKGROUND: Typhoid is endemic in many low-income countries, including in Papua New Guinea. This study aimed to describe the burden and clinical features of typhoid in children in a provincial hospital, to describe environmental conditions that lead to typhoid, and to document the antibiotic sensitivity of Salmonella spp. in the Eastern Highlands Province. METHODS: A combined retrospective and prospective study of children admitted to with clinical features of typhoid to the Goroka Hospital throughout 2022. RESULTS: The study included 98 children, of which 54% were female. The median age was 8 (IQR 5-10.6) years. Over 60% of the patients were from Goroka District, the peri-urban area encompassing the town and surrounds. Ninety-four percent (92) of the patients used a pit latrine as a toilet and only 28% had access to treated water. Neuropsychiatric symptoms were common (60%), as was leukopenia (48%), thrombocytopenia (52%) and anaemia (42%). Thirty-seven patients had positive blood cultures for Salmonella typhi; all isolates were sensitive to third-generation cephalosporins, pefloxacin, ampicillin, trimethoprim and sulfamethoxazole, and only 54% sensitive to chloramphenicol. The median duration of hospitalisation was 6 days (IQR). There were no deaths. CONCLUSION: Prompt public health actions are needed to reduce the burden of typhoid infection in the Papua New Guinea. The conjugate typhoid vaccine should be considered in the highlands region, where typhoid is most endemic.


Assuntos
Febre Tifoide , Humanos , Febre Tifoide/epidemiologia , Febre Tifoide/tratamento farmacológico , Febre Tifoide/diagnóstico , Papua Nova Guiné/epidemiologia , Feminino , Masculino , Criança , Pré-Escolar , Estudos Retrospectivos , Estudos Prospectivos , Salmonella typhi/isolamento & purificação , Salmonella typhi/efeitos dos fármacos , Antibacterianos/uso terapêutico
11.
PLoS Negl Trop Dis ; 18(4): e0012132, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38630840

RESUMO

BACKGROUND: Typhoid fever is a common cause of febrile illness in low- and middle-income countries. While multidrug-resistant (MDR) Salmonella Typhi (S. Typhi) has spread globally, fluoroquinolone resistance has mainly affected Asia. METHODS: Consecutively, 1038 blood cultures were obtained from patients of all age groups with fever and/or suspicion of serious systemic infection admitted at Mnazi Mmoja Hospital, Zanzibar in 2015-2016. S. Typhi were analyzed with antimicrobial susceptibility testing and with short read (61 strains) and long read (9 strains) whole genome sequencing, including three S. Typhi strains isolated in a pilot study 2012-2013. RESULTS: Sixty-three S. Typhi isolates (98%) were MDR carrying blaTEM-1B, sul1 and sul2, dfrA7 and catA1 genes. Low-level ciprofloxacin resistance was detected in 69% (43/62), with a single gyrase mutation gyrA-D87G in 41 strains, and a single gyrA-S83F mutation in the non-MDR strain. All isolates were susceptible to ceftriaxone and azithromycin. All MDR isolates belonged to genotype 4.3.1 lineage I (4.3.1.1), with the antimicrobial resistance determinants located on a composite transposon integrated into the chromosome. Phylogenetically, the MDR subgroup with ciprofloxacin resistance clusters together with two external isolates. CONCLUSIONS: We report a high rate of MDR and low-level ciprofloxacin resistant S. Typhi circulating in Zanzibar, belonging to genotype 4.3.1.1, which is widespread in Southeast Asia and African countries and associated with low-level ciprofloxacin resistance. Few therapeutic options are available for treatment of typhoid fever in the study setting. Surveillance of the prevalence, spread and antimicrobial susceptibility of S. Typhi can guide treatment and control efforts.


Assuntos
Antibacterianos , Ciprofloxacina , Farmacorresistência Bacteriana Múltipla , Genótipo , Testes de Sensibilidade Microbiana , Salmonella typhi , Febre Tifoide , Humanos , Salmonella typhi/genética , Salmonella typhi/efeitos dos fármacos , Salmonella typhi/isolamento & purificação , Salmonella typhi/classificação , Ciprofloxacina/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Antibacterianos/farmacologia , Febre Tifoide/microbiologia , Febre Tifoide/epidemiologia , Tanzânia/epidemiologia , Adolescente , Masculino , Criança , Adulto , Adulto Jovem , Feminino , Pré-Escolar , Sequenciamento Completo do Genoma , Pessoa de Meia-Idade , Lactente , Idoso
12.
Expert Opin Ther Targets ; 28(4): 323-334, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38639582

RESUMO

OBJECTIVES: Salmonella Typhibiofilm condition is showing as a major public health problem due to the development of antibiotic resistance and less available druggable target proteins. Therefore, we aimed to identify some more druggable targets of S. Typhibiofilm using computational drilling at the genome/proteome level so that the target shortage problem could be overcome and more antibiofilm agents could be designed in the future against the disease. METHODS: We performed protein-protein docking and interaction analysis between the homological identified target proteins of S.Typhi biofilm and a therapeutic protein L-Asparaginase. RESULTS: We have identified some druggable targets CsgD, BcsA, OmpR, CsgG, CsgE, and CsgF in S.Typhi. These targets showed high-binding affinity BcsA (-219.8 Kcal/mol) >csgF (-146.52 Kcal/mol) >ompR (-135.68 Kcal/mol) >CsgE (-134.66 Kcal/mol) >CsgG (-113.81 Kcal/mol) >CsgD(-95.39 Kcal/mol) with therapeutic enzyme L-Asparaginase through various hydrogen-bonds and salt-bridge. We found six proteins of S. Typhi biofilm from the Csg family as druggable multiple targets. CONCLUSION: This study provides insight into the idea of identification of new druggable targets and their multiple targeting with L-Asparaginase to overcome target shortage in S. Typhibiofilm-mediated infections. Results further indicated that L-Asparaginase could potentially be utilized as an antibiofilm biotherapeutic agent against S.Typhi.


Assuntos
Antibacterianos , Asparaginase , Biofilmes , Simulação de Acoplamento Molecular , Salmonella typhi , Biofilmes/efeitos dos fármacos , Asparaginase/farmacologia , Asparaginase/isolamento & purificação , Salmonella typhi/efeitos dos fármacos , Humanos , Antibacterianos/farmacologia , Proteínas de Bactérias/metabolismo , Desenho de Fármacos , Terapia de Alvo Molecular , Farmacorresistência Bacteriana
13.
Diagn Microbiol Infect Dis ; 109(3): 116276, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38613950

RESUMO

Salmonella enterica serotype Typhi (S Typhi) associated urinary tract infections are exceedingly rare, accounting for less than 1% of cases. Such infections have known to occur in immune-compromised or individuals with urogenital structural abnormalities. With the emergence of extensively drug resistant S Typhi strains in Pakistan, the management of its various unique presentations poses therapeutic challenges. We report the first documented case of a 74 years old male patient presenting with relapsed urinary tract infection secondary to extensively drug resistant S Typhi.


Assuntos
Antibacterianos , Farmacorresistência Bacteriana Múltipla , Recidiva , Salmonella typhi , Febre Tifoide , Infecções Urinárias , Humanos , Masculino , Salmonella typhi/efeitos dos fármacos , Salmonella typhi/isolamento & purificação , Infecções Urinárias/microbiologia , Infecções Urinárias/tratamento farmacológico , Febre Tifoide/microbiologia , Febre Tifoide/tratamento farmacológico , Idoso , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Paquistão , Testes de Sensibilidade Microbiana
14.
Ir J Med Sci ; 193(3): 1377-1384, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38158479

RESUMO

BACKGROUND: Typhoid fever is a fatal disease in humans that is caused by Salmonella typhi. S. typhi infections need immediate antibiotic therapy, and their extensive use has led to multidrug-resistant (MDR) pathogens. The use of bacteriophages is becoming a new way to treat these resistant bacteria. This research was directed to bacteriophage isolation against S. typhi and to determine phage-antibiotic synergism. AIMS: To isolate bacteriophages targeting S. typhi, the causative agent of typhoid fever, and investigate their potential synergistic effects when combined with antibiotics. STUDY DESIGN: A cross-sectional study. METHODS: The Widal test was positive; twenty diarrheal stool samples were taken, and for confirmation of S. typhi, different biochemical tests were performed. The disc-diffusion technique was used to determine antimicrobial resistance, and the double agar overlay method was used for bacteriophage isolation from sewage water against S. typhi. To test antibiotic-phage synergism, the S. typhi bacteria was treated by phages together with varying antibiotic concentrations. RESULTS: Eleven samples were positive for S. typhi with black colonies on SS-agar. These were catalase and MR positive with alkali butt on TSI. Clear plaques were observed after the agar overlay. Isolated phages were stable at various pH and temperature levels. Synergism was observed on agar plate. The zone was enlarged when phages were combined with bacterial lawn culture and ciprofloxacin disk. Bacterial growth inhibition had a significant p-value of 0.03 in titration plates, with the phage-ciprofloxacin combination being more effective than the phage and antibiotic alone. CONCLUSION: The study highlights the synergistic effects of isolated bacteriophages with antibiotics, which are not only effective against S. typhi infection but also decrease antibiotic resistance.


Assuntos
Antibacterianos , Fezes , Salmonella typhi , Febre Tifoide , Salmonella typhi/efeitos dos fármacos , Salmonella typhi/isolamento & purificação , Humanos , Febre Tifoide/microbiologia , Febre Tifoide/tratamento farmacológico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Estudos Transversais , Fezes/microbiologia , Fezes/virologia , Bacteriófagos/isolamento & purificação , Testes de Sensibilidade Microbiana , Terapia por Fagos/métodos
15.
BMC Microbiol ; 23(1): 25, 2023 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-36681806

RESUMO

Typhoid fever is transmitted by ingestion of polluted water, contaminated food, and stool of typhoid-infected individuals, mostly in developing countries with poor hygienic environments. To find novel therapeutic targets and inhibitors, We employed a subtractive genomics strategy towards Salmonella Typhi and the complete genomes of eight strains were primarily subjected to the EDGAR tool to predict the core genome (n = 3207). Human non-homology (n = 2450) was followed by essential genes identification (n = 37). The STRING database predicted maximum protein-protein interactions, followed by cellular localization. The virulent/immunogenic ability of predicted genes were checked to differentiate drug and vaccine targets. Furthermore, the 3D models of the identified putative proteins encoded by the respective genes were constructed and subjected to druggability analyses where only "highly druggable" proteins were selected for molecular docking and simulation analyses. The putative targets ATP-dependent CLP protease proteolytic subunit, Imidazole glycerol phosphate synthase hisH, 7,8-dihydropteroate synthase folP and 2,3-bisphosphoglycerate-independent phosphoglycerate mutase gpmI were screened against a drug-like library (n = 12,000) and top hits were selected based on H-bonds, RMSD and energy scores. Finally, the ADMET properties for novel inhibitors ZINC19340748, ZINC09319798, ZINC00494142, ZINC32918650 were optimized followed by binding free energy (MM/PBSA) calculation for ligand-receptor complexes. The findings of this work are expected to aid in expediting the identification of novel protein targets and inhibitors in combating typhoid Salmonellosis, in addition to the already existing therapies.


Assuntos
Antibacterianos , Salmonella typhi , Humanos , Antibacterianos/farmacologia , Antibacterianos/química , Endopeptidase Clp , Genômica , Simulação de Acoplamento Molecular , Salmonella typhi/efeitos dos fármacos , Salmonella typhi/genética , Febre Tifoide
16.
Afr Health Sci ; 23(4): 177-182, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38974275

RESUMO

Background: The emanation of multi-drugs resistant microorganisms and the challenges faced in combating multi-drug resistant infections is a public health issue and this has increased the search for effective antibiotics from natural sources. Objectives: This work aims to determine the susceptibility of some pathogenic bacterial species to snail slime. Methods: The antibacterial activity of aqueous and ethanolic snail slime extracts were investigated against Staphylococcus aureus, Salmonella typhi, Bacillus subtilis and Escherichia coli using the agar well diffusion method. Results: The results showed that all the organisms were sensitive to both extracts but were more susceptible to aqueous extracts; the highest zone of inhibition for aqueous extracts was 27.33mm ± 2.51mm for Staphylococcus aureus at concentration of 1000µl/ml, while the lowest was 11.33mm ± 1.53mm against Escherichia coli. The highest zone of inhibition for ethanolic fraction was 15.67 ± 1.15mm for Salmonella typhi. The lowest inhibition was 9.33mm ± 0.58mm for Escherichia coli. The MIC was 3.125% for Staphylococcus aureus, Bacillus subtilis and Escherichia coli and 6.25% for S. typhi. The extracts were not cidal at the concentrations used. Statistical analysis revealed that the treatments between the aqueous and ethanolic extracts against Staphylococcus aureus, Escherichia coli and Salmonella typhi were significant (p ≤ 0.05). The treatment against B. subtilis showed no significant difference between the two extracts (p > 0.05). Conclusion: This study has revealed that snail slime possesses antibacterial properties which can be used as anti-microbial agents against infectious diseases.


Assuntos
Antibacterianos , Bacillus subtilis , Escherichia coli , Testes de Sensibilidade Microbiana , Salmonella typhi , Caramujos , Staphylococcus aureus , Escherichia coli/efeitos dos fármacos , Salmonella typhi/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Animais , Caramujos/microbiologia , Humanos
17.
World J Microbiol Biotechnol ; 38(11): 190, 2022 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-35972699

RESUMO

Multi-drug resistance (MDR) in Salmonella is one of the major reasons for foodborne outbreaks worldwide. Decreased susceptibility of Salmonella Typhi to first-line drugs such as ceftriaxone, ciprofloxacin, and azithromycin has raised concern. Reduced outer membrane proteins (OMPs) permeability and increased efflux pump transportation are considered to be the main reasons for the emergence of antibiotic resistance in Salmonella. The present study aimed to assess the expression of OMPs at sub-lethal concentrations of ceftriaxone in S. Typhi (Sl5037/BC, and Sl05). The S. Typhi strains were exposed to sub-MIC and half of the sub-MIC concentrations of ceftriaxone at three different time intervals (0 min, 40 min, and 180 min) and analyzed for differential expression of OMPs. Further, the expression variation of OMP encoding genes (yaeT, ompX, lamb, ompA, and ybfM) in response to ceftriaxone was evaluated using real-time PCR. The genes like lamB, ompX, and yaeT showed significant downregulation (p < 0.05) compared to the control without antibiotic exposure, whereas ybfM and ompA showed a moderate downregulation. The expression of omp genes such as lamB, ompA, ompX, ybfM, and yaeT were found to be low in the presence of ceftriaxone, followed by time and dose-dependent. The study provides insights into the possible involvement of OMPs in drug resistance of S. Typhi, which could help develop a therapeutic strategy to combat MDR isolates of S. Typhi.


Assuntos
Antibacterianos , Proteínas da Membrana Bacteriana Externa , Ceftriaxona , Salmonella typhi , Antibacterianos/farmacologia , Proteínas da Membrana Bacteriana Externa/metabolismo , Ceftriaxona/farmacologia , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana , Salmonella typhi/efeitos dos fármacos
18.
Microb Drug Resist ; 28(1): 120-126, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34357814

RESUMO

Objective: To determine the molecular strain typing and drug resistance pattern of Salmonella enterica serovar Typhi prevalent in Northwest Pakistan. Methodology: A total of 2,138 blood samples of suspected typhoid patients from Northwest Pakistan were collected followed by identification of Salmonella Typhi through biochemical, serological, and species-specific fliC-d gene amplification. These isolates were typed by variable-number tandem repeat (VNTR) profiling and investigated for drug resistance. Results: The overall prevalence of Salmonella Typhi was found to be 8.8% (n = 189). Thirty different VNTR strain types of Salmonella Typhi were detected and the most prevalent strain types were T1 and T4, whereas T27 was less prevalent strain. Among the 189 isolates 175 (92.5%) isolates were multidrug resistant, whereas 12 (5.8%) isolates were extensively drug resistant. Resistance to imipenem in Salmonella Typhi was not observed. Most of the isolates have genes encoding for resistance to fluoroquinolones, including gyrA (n = 164), gyrB (n = 160), parC (n = 164), parE (n = 160), ac(6')-ib-cr (n = 163), qnrS (n = 15), and qnrB (n = 3). Similarly, chloramphinicol (cat; n = 147), azithromycin (msrA; n = 3), and co-trimoxazole (dfrA7; n = 145) resistance genes were detected among Salmonella Typhi isolates. Conclusion: In this study, T1 and T4 type Salmonella Typhi strains were predominantly prevalent in Northwest Pakistan. Antibiotic resistance among Salmonella Typhi isolates were observed. Findings of the study would be helpful to devise an appropriate antibiotic policy to control the emergence of drug-resistant Salmonella Typhi in Pakistan.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Salmonella typhi/efeitos dos fármacos , Salmonella typhi/genética , Infecção Hospitalar/genética , Genes Bacterianos , Humanos , Testes de Sensibilidade Microbiana , Repetições Minissatélites , Tipagem Molecular , Paquistão , Centros de Atenção Terciária
19.
Clin Infect Dis ; 74(12): 2234-2237, 2022 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34626469

RESUMO

We report the persistent circulation of third-generation cephalosporin resistant Salmonella Typhi in Mumbai, linked to the acquisition and maintenance of a previously characterized IncX3 plasmid carrying the ESBL gene blaSHV-12 and the fluoroquinolone resistance gene qnrB7 in the genetic context of a triple mutant also associated with fluoroquinolone resistance.


Assuntos
Antibacterianos , Farmacorresistência Bacteriana , Salmonella typhi , Antibacterianos/farmacologia , Cefalosporinas/farmacologia , Fluoroquinolonas , Humanos , Índia/epidemiologia , Testes de Sensibilidade Microbiana , Salmonella typhi/efeitos dos fármacos , Salmonella typhi/genética , beta-Lactamases/genética
20.
Pan Afr Med J ; 40: 58, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34795837

RESUMO

INTRODUCTION: Marsdenia macrantha is a crucial source of traditional medicine in Northern Namibia. Its roots are used to treat various health conditions ranging from mouth infections to urinary retention. Despite its medicinal application, there is no known knowledge of its therapeutic properties. Thus, we investigated the phytochemical content and antibacterial activity of M. macrantha. METHODS: M. macrantha root extracts were obtained using three different solvents (distilled water, methanol and acetone) - in the soxhlet and maceration extraction methods. Total phytochemical (terpenoid, alkaloid and/or flavonoid) content was determined by spectrophotometry. Antibacterial activity against common foodborne pathogens (Staphylococcus aureus, Escherichia coli and Salmonella typhi) was determined by both well and disc diffusion method. RESULTS: we detected the presence of all the tested phytochemicals. Methanol gave the highest percentage yield of extraction (mean: 13.95 ± standard deviation: 0.41%) followed by water (10.92 ± 0.11%) and acetone (6.85 ± 0.23%), F-ratio=326.71 and p<0.0003. The total content determined showed that M. macrantha root extract contained more flavonoids than alkaloids (mg of standard per grams of the dry material). Antibacterial analyses showed inhibitory activity against all the selected pathogens, with the highest inhibition zone against S. typhi (19.7 ± 0.3 mm) - for the acetone-prepared root extract. There were variations in minimum inhibitory concentrations of the extracts prepared by the different solvents. CONCLUSION: this is the first study demonstrating the presence of phytochemicals and antibacterial properties of M. macrantha roots. Further studies are needed to isolate and characterize the phytochemicals for antibacterial application.


Assuntos
Antibacterianos/farmacologia , Marsdenia/química , Extratos Vegetais/farmacologia , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Antibacterianos/isolamento & purificação , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Escherichia coli/efeitos dos fármacos , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Testes de Sensibilidade Microbiana , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Raízes de Plantas , Salmonella typhi/efeitos dos fármacos , Solventes/química , Staphylococcus aureus/efeitos dos fármacos , Terpenos/isolamento & purificação , Terpenos/farmacologia
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