ABSTRACT
Effective molecular strategies are needed to target pathogenic bacteria that thrive and proliferate within mammalian cells, a sanctuary inaccessible to many therapeutics. Herein, we present a class of cationic amphiphilic polyproline helices (CAPHs) with a rigid placement of the cationic moiety on the polyproline helix and assess the role of configuration of the unnatural proline residues making up the CAPHs. By shortening the distance between the guanidinium side chain and the proline backbone of the agents, a notable increase in cellular uptake and antibacterial activity was observed, whereas changing the configuration of the moieties on the pyrrolidine ring from cis to trans resulted in more modest increases. When the combination of these two activities was evaluated, the more rigid CAPHs were exceptionally effective at eradicating intracellular methicillin-resistant Staphylococcus aureus (MRSA) and Salmonella infections within macrophages, significantly exceeding the clearance with the parent CAPH.
Subject(s)
Anti-Bacterial Agents , Methicillin-Resistant Staphylococcus aureus , Peptides , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Animals , Methicillin-Resistant Staphylococcus aureus/drug effects , Mice , Peptides/chemistry , Peptides/pharmacology , Macrophages/drug effects , Microbial Sensitivity Tests , Cations/chemistry , Cations/pharmacology , Antimicrobial Cationic Peptides/pharmacology , Antimicrobial Cationic Peptides/chemistry , Humans , Salmonella Infections/microbiology , Salmonella Infections/drug therapy , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiologyABSTRACT
RATIONALE: Bacterascites are a rare complication of cesarean sections (C/S). Here, we report the case of a patient with bacterascites after an emergent C/S. PATIENT CONCERN: A 41-year-old female reported diffuse abdominal tightness and pain for a week after C/S, who received C/S at 38 4/7 weeks due to superimposed preeclampsia and prolonged labor. DIAGNOSES: Bacterascites caused by Salmonella species after C/S was diagnosed. INTERVENTIONS: Initial treatment included cefmetazole and metronidazole. On day 2, paracentesis was performed, followed by albumin and hydroxyethyl starch administration. By day 3, the patient developed pulmonary edema, necessitating Lasix administration. On day 6, ascites culture revealed Salmonella species resistant to third-generation cephalosporins, leading to meropenem therapy adjustment. This resulted in improved symptoms. Meropenem was continued for 14 days to complete the treatment regimen. OUTCOMES: Follow-up ultrasonography revealed a decrease in ascites. As the patient clinical condition improved, she was discharged on day 20 and scheduled for outpatient department follow-up. No recurrence of ascites was observed during the subsequent follow-up period of 3 months. No ascites were noted 8 days after discharge. LESSONS: Postoperative bacterascites with Salmonella were diagnosed. Antibiotic treatment and therapeutic paracentesis were effective for this condition.
Subject(s)
Anti-Bacterial Agents , Cesarean Section , Salmonella Infections , Salmonella , Humans , Female , Adult , Cesarean Section/adverse effects , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/administration & dosage , Salmonella/isolation & purification , Salmonella Infections/diagnosis , Salmonella Infections/drug therapy , Pregnancy , Meropenem/therapeutic use , Meropenem/administration & dosage , Ascites/etiology , Ascites/microbiology , Bacteremia/microbiology , Bacteremia/drug therapy , Postoperative Complications/microbiology , Paracentesis/methodsABSTRACT
BACKGROUND: Abdominal aorta-duodenal fistulas are rare abnormal communications between the abdominal aorta and duodenum. Secondary abdominal aorta-duodenal fistulas often result from endovascular surgery for aneurysms and can present as severe late complications. CASE PRESENTATION: A 50-year-old male patient underwent endovascular reconstruction for an infrarenal abdominal aortic pseudoaneurysm. Prior to the operation, he was diagnosed with Acquired Immune Deficiency Syndrome and Syphilis. Two years later, he was readmitted with lower extremity pain and fever. Blood cultures grew Enterococcus faecium, Salmonella, and Streptococcus anginosus. Sepsis was successfully treated with comprehensive anti-infective therapy. He was readmitted 6 months later, with blood cultures growing Enterococcus faecium and Escherichia coli. Although computed tomography did not show contrast agent leakage, we suspected an abdominal aorta-duodenal fistula. Esophagogastroduodenoscopy confirmed this suspicion. The patient underwent in situ abdominal aortic repair and received long-term antibiotic therapy. He remained symptom-free during a year and a half of follow-up. CONCLUSIONS: This case suggests that recurrent infections with non-typhoidal Salmonella and gut bacteria may be an initial clue to secondary abdominal aorta-duodenal fistula.
Subject(s)
Sepsis , Humans , Male , Middle Aged , Sepsis/microbiology , Sepsis/complications , Aorta, Abdominal/surgery , Aorta, Abdominal/microbiology , Enterococcus faecium/isolation & purification , Anti-Bacterial Agents/therapeutic use , Streptococcus anginosus/isolation & purification , Intestinal Fistula/microbiology , Intestinal Fistula/surgery , Intestinal Fistula/complications , Salmonella/isolation & purification , Escherichia coli/isolation & purification , Recurrence , Duodenal Diseases/microbiology , Duodenal Diseases/surgery , Duodenal Diseases/complications , Salmonella Infections/microbiology , Salmonella Infections/complications , Salmonella Infections/diagnosis , Salmonella Infections/drug therapyABSTRACT
The emergence of antimicrobial resistance has created an urgent need for alternative treatments against bacterial pathogens. Here, we investigated kinase inhibitors as potential host-directed therapies (HDTs) against intracellular bacteria, specifically Salmonella Typhimurium (Stm) and Mycobacterium tuberculosis (Mtb). We screened 827 ATP-competitive kinase inhibitors with known target profiles from two Published Kinase Inhibitor Sets (PKIS1 and PKIS2) using intracellular infection models for Stm and Mtb, based on human cell lines and primary macrophages. Additionally, the in vivo safety and efficacy of the compounds were assessed using zebrafish embryo infection models. Our screen identified 11 hit compounds for Stm and 17 hit compounds for Mtb that were effective against intracellular bacteria and non-toxic for host cells. Further experiments were conducted to prioritize Stm hit compounds that were able to clear the intracellular infection in primary human macrophages. From these, two structurally related Stm hit compounds, GSK1379738A and GSK1379760A, exhibited significant activity against Stm in infected zebrafish embryos. In addition, we identified compounds that were active against intracellular Mtb, including morpholino-imidazo/triazolo-pyrimidinones that target PIK3CB, as well as 2-aminobenzimidazoles targeting ABL1. Overall, this study provided insights into kinase targets acting at the host-pathogen interface and identified several kinase inhibitors as potential HDTs.
Subject(s)
Macrophages , Mycobacterium tuberculosis , Protein Kinase Inhibitors , Salmonella typhimurium , Zebrafish , Animals , Humans , Salmonella typhimurium/drug effects , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/enzymology , Protein Kinase Inhibitors/pharmacology , Macrophages/microbiology , Macrophages/drug effects , Macrophages/metabolism , Salmonella Infections/drug therapy , Salmonella Infections/microbiology , Anti-Bacterial Agents/pharmacology , Cell Line , Embryo, Nonmammalian/drug effects , Tuberculosis/drug therapy , Tuberculosis/microbiologyABSTRACT
The vast dissemination of resistance to different antibiotics among bacterial pathogens, especially foodborne pathogens, has drawn major research attention. Thus, many attempts have been made to reveal novel alternatives to the current antibiotics. Due to their variable pharmacologically active phytochemicals, plants represent a good solution for this issue. This study investigated the antibacterial potential of Kumquat or Fortunella japonica methanol extract (FJME) against Salmonella typhimurium clinical isolates. Gas chromatography coupled with mass spectrometry (GC/MS) characterized 39 compounds in FJME. Palmitic acid (15.386%) and cis-vaccenic acid (15.012%) are the major active constituents detected by GC/MS. Remarkably, FJME had minimum inhibitory concentrations from 128 to 512 µg/mL in vitro. In addition, a systemic infection model revealed the in vivo antibacterial action of FJME. The antibacterial therapeutic activity of FJME was noticed by improving the histological features of the liver and spleen. Moreover, there was a perceptible lessening (p < 0.05) of the levels of the oxidative stress markers (nitric oxide and malondialdehyde) using ELISA. In addition, the gene expression of the proinflammatory cytokine (interleukin 6) was downregulated. On the other hand, there was an upregulation of the anti-inflammatory cytokine (interleukin 10). Accordingly, future clinical investigations should be done to reveal the potential antibacterial action of FJME on other food pathogens.
Subject(s)
Anti-Bacterial Agents , Fruit , Microbial Sensitivity Tests , Plant Extracts , Salmonella typhimurium , Plant Extracts/pharmacology , Plant Extracts/chemistry , Salmonella typhimurium/drug effects , Anti-Bacterial Agents/pharmacology , Fruit/microbiology , Fruit/chemistry , Animals , Mice , Salmonella Infections/microbiology , Salmonella Infections/drug therapyABSTRACT
A man in his mid-70s with a complex medical history, including splenectomy, presented with fever and rigours. Workup revealed Salmonella enterica serotype typhimurium bacteraemia and right internal iliac artery endarteritis. Two weeks following a 6-week course of antibiotics, he had a recurrence of Salmonella bacteraemia requiring an extended course of treatment.
Subject(s)
Anti-Bacterial Agents , Bacteremia , Endarteritis , Iliac Artery , Salmonella Infections , Splenectomy , Humans , Male , Salmonella Infections/complications , Salmonella Infections/diagnosis , Salmonella Infections/drug therapy , Bacteremia/drug therapy , Bacteremia/complications , Bacteremia/microbiology , Iliac Artery/diagnostic imaging , Anti-Bacterial Agents/therapeutic use , Aged , Recurrence , Salmonella typhimurium/isolation & purificationABSTRACT
We report a severe case of a 25-year-old girl presented with complaints of weakness, diarrhoea, vomiting, pain in abdomen and hypotension at Infectious Diseases and Clinical Immunology Research Center. From history on 25 February till 29 February she was in India and on 1 march this problem started with watery diarrhoea followed by vomiting. She ate pizza with mushroom following which her condition worsened. Stool culture revealed salmonella nontyphi (nonthyphodal Salmonella)and this is leading cause for gastroenteritis, bacteremia and affects several other bodily system. Her condition deteriorated due to the development of ARDS (acute respiratory distress syndrome) and for this she was on mechanical ventilation. Vitec machine was performed, which identified Salmonella typhi murium. Our goal is to manage and treat this patient well by early diagnosis. She was given ceftriaxone, iv fluids and symptomatic treatment but due to resistance meropenem was started and the patient's condition improved. From serology there was no evidence of immunocompromised state so being a severe case of immunocompetent patient this case reflects the importance of timely diagnosis and management together with food safety practices in population. On follow up she was stable and discharged after 3 weeks. Future research studies need to be continued regarding newer strains, effective treatment strategies and diagnostics to prevent morbidity and mortality.
Subject(s)
Salmonella Infections , Adult , Female , Humans , Anti-Bacterial Agents/therapeutic use , Ceftriaxone/therapeutic use , Diarrhea/microbiology , Meropenem/therapeutic use , Multiple Organ Failure/microbiology , Multiple Organ Failure/etiology , Respiratory Distress Syndrome/microbiology , Respiratory Distress Syndrome/etiology , Salmonella Infections/diagnosis , Salmonella Infections/drug therapy , Salmonella Infections/microbiology , Salmonella Infections/complications , Salmonella typhimurium/isolation & purificationABSTRACT
MccY is a novel, structurally stable microcin with antibacterial activity against Enterobacteriaceae. However, the bioavailability of orally administrated MccY is unknown. This study evaluated the effects of MccY as a antimicrobial on pre-digestion in vitro and its intake, digestion and gut metabolism in vivo. The result of pre-digestion results that MccY maintained its biological activity and was resistant to decomposition. The study established a safe threshold of 4.46-9.92 mg/kg for the MccY dosage-body weight relationship in BALB/c mice. Mice fed with MccY demonstrated improved body weight and intestinal barrier function, accompanied with increased IgM immunogenicity and decreased levels of TNF-α, IL-6, and IL-10 in the intestine. MccY significantly facilitates the growth and activity of probiotics including Lactobacillus, Prevotella, and Bacteroides, and leading to the production of SCFAs and MCFAs during bacterial interactions. Furthermore, MccY effectively protects against the inflammatory response caused by Salmonella Typhimurium infection and effectively clears the Salmonella bacteria from the gut. In conclusion, MccY is seen as a promising new therapeutic target drug for enhancing the intestinal microbe-barrier axis and preventing enteritis.
Subject(s)
Bacteriocins , Gastrointestinal Microbiome , Mice, Inbred BALB C , Probiotics , Animals , Probiotics/pharmacology , Mice , Bacteriocins/pharmacology , Bacteriocins/chemistry , Gastrointestinal Microbiome/drug effects , Salmonella typhimurium/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Salmonella Infections/drug therapy , Intestines/microbiology , Intestines/drug effectsABSTRACT
BACKGROUND: The upsurge of antimicrobial resistance demands innovative strategies to fight bacterial infections. With traditional antibiotics becoming less effective, anti-virulence agents or pathoblockers, arise as an alternative approach that seeks to disarm pathogens without affecting their viability, thereby reducing selective pressure for the emergence of resistance mechanisms. OBJECTIVES: To elucidate the mechanism of action of compound N'-(thiophen-2-ylmethylene)benzohydrazide (A16B1), a potent synthetic hydrazone inhibitor against the Salmonella PhoP/PhoQ system, essential for virulence. MATERIALS AND METHODS: The measurement of the activity of PhoP/PhoQ-dependent and -independent reporter genes was used to evaluate the specificity of A16B1 to the PhoP regulon. Autokinase activity assays with either the native or truncated versions of PhoQ were used to dissect the A16B1 mechanism of action. The effect of A16B1 on Salmonella intramacrophage replication was assessed using the gentamicin protection assay. The checkerboard assay approach was used to analyse potentiation effects of colistin with the hydrazone. The Galleria mellonella infection model was chosen to evaluate A16B1 as an in vivo therapy against Salmonella. RESULTS: A16B1 repressed the Salmonella PhoP/PhoQ system activity, specifically targeting PhoQ within the second transmembrane region. A16B1 demonstrates synergy with the antimicrobial peptide colistin, reduces the intramacrophage proliferation of Salmonella without being cytotoxic and enhances the survival of G. mellonella larvae systemically infected with Salmonella. CONCLUSIONS: A16B1 selectively inhibits the activity of the Salmonella PhoP/PhoQ system through a novel inhibitory mechanism, representing a promising synthetic hydrazone compound with the potential to function as a Salmonella pathoblocker. This offers innovative prospects for combating Salmonella infections while mitigating the risk of antimicrobial resistance emergence.
Subject(s)
Anti-Bacterial Agents , Bacterial Proteins , Salmonella Infections , Animals , Bacterial Proteins/antagonists & inhibitors , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Salmonella Infections/drug therapy , Salmonella Infections/microbiology , Moths/microbiology , Disease Models, Animal , Salmonella typhimurium/drug effects , Salmonella typhimurium/genetics , Colistin/pharmacology , Microbial Sensitivity Tests , Hydrazones/pharmacology , Hydrazones/therapeutic use , Drug Synergism , Virulence/drug effects , Histidine Kinase/antagonists & inhibitors , Histidine Kinase/genetics , Allosteric Regulation/drug effectsABSTRACT
Salmonella enteritidis is a main pathogen responsible for sporadic outbreaks of gastroenteritis, and therefore is an important public health problem. This study investigated the drug resistance and genomic characteristics of S. enteritidis isolated from clinical and food sources in Huzhou, Zhejiang Province, China, from February 1, 2021, to December 30, 2023. In total, 43 S. enteritidis strains isolated during the study period were subjected to virulence gene, drug resistance gene, genetic correlation, antibiotic resistance, and multilocus sequence typing analyses. All 43 isolates were identified as ST11, and contained 108 virulence-related genes. Drug sensitivity analysis of the 43 isolates showed resistance rates of 100% to nalidixic acid and 90.70% to ampicillin and ampicillin/sulbactam. Multidrug resistance is a serious issue, with 81.40% of strains resistant to three or more antibacterial drugs. Genome sequencing indicated that S. enteritidis possessed 23 drug resistance genes, of which 14 were common to all 43 isolates. Phylogenetic analysis based on core genome single-nucleotide polymorphisms divided the 43 S. enteritidis strains into three clusters, with the 10 samples from an outbreak forming an independent branch located in cluster 3.
Subject(s)
Anti-Bacterial Agents , Genome, Bacterial , Phylogeny , Salmonella enteritidis , Salmonella enteritidis/genetics , Salmonella enteritidis/drug effects , Salmonella enteritidis/isolation & purification , China/epidemiology , Anti-Bacterial Agents/pharmacology , Humans , Multilocus Sequence Typing , Microbial Sensitivity Tests , Salmonella Infections/microbiology , Salmonella Infections/epidemiology , Salmonella Infections/drug therapy , Drug Resistance, Multiple, Bacterial/genetics , Polymorphism, Single Nucleotide , Drug Resistance, Bacterial/genetics , Whole Genome SequencingABSTRACT
Antimicrobial resistance (AMR) is a growing public health crisis that requires innovative solutions. Current susceptibility testing approaches limit our ability to rapidly distinguish between antimicrobial-susceptible and -resistant organisms. Salmonella Typhimurium (S. Typhimurium) is an enteric pathogen responsible for severe gastrointestinal illness and invasive disease. Despite widespread resistance, ciprofloxacin remains a common treatment for Salmonella infections, particularly in lower-resource settings, where the drug is given empirically. Here, we exploit high-content imaging to generate deep phenotyping of S. Typhimurium isolates longitudinally exposed to increasing concentrations of ciprofloxacin. We apply machine learning algorithms to the imaging data and demonstrate that individual isolates display distinct growth and morphological characteristics that cluster by time point and susceptibility to ciprofloxacin, which occur independently of ciprofloxacin exposure. Using a further set of S. Typhimurium clinical isolates, we find that machine learning classifiers can accurately predict ciprofloxacin susceptibility without exposure to it or any prior knowledge of resistance phenotype. These results demonstrate the principle of using high-content imaging with machine learning algorithms to predict drug susceptibility of clinical bacterial isolates. This technique may be an important tool in understanding the morphological impact of antimicrobials on the bacterial cell to identify drugs with new modes of action.
Subject(s)
Anti-Bacterial Agents , Ciprofloxacin , Drug Resistance, Bacterial , Machine Learning , Microbial Sensitivity Tests , Salmonella typhimurium , Ciprofloxacin/pharmacology , Salmonella typhimurium/drug effects , Salmonella typhimurium/isolation & purification , Anti-Bacterial Agents/pharmacology , Humans , Salmonella Infections/microbiology , Salmonella Infections/drug therapy , AlgorithmsABSTRACT
Salmonella 4,[5],12:i:-, a monophasic variant of Salmonella Typhimurium, has emerged as a global cause of multidrug-resistant salmonellosis and has become endemic in many developing and developed countries, especially in China. Here, we have sequenced 352 clinical isolates in Guangdong, China, during 2009-2019 and performed a large-scale collection of Salmonella 4,[5],12:i:- with whole genome sequencing (WGS) data across the globe, to better understand the population structure, antimicrobial resistance (AMR) genomic characterization, and transmission routes of Salmonella 4,[5],12:i:- across Guangdong. Salmonella 4,[5],12:i:- strains showed broad genetic diversity; Guangdong isolates were found to be widely distributed among the global lineages. Of note, we identified the formation of a novel Guangdong clade (Bayesian analysis of population structure lineage 1 [BAPS1]) genetically diversified from the global isolates and likely emerged around 1990s. BAPS1 exhibits unique genomic features, including large pan-genome, decreased ciprofloxacin susceptibility due to mutation in gyrA and carriage of plasmid-mediated quinolone resistance (PMQR) genes, and the multidrug-resistant IncHI2 plasmid. Furthermore, high genetic similarity was found between strains collected from Guangdong, Europe, and North America, indicating the association with multiple introductions from overseas. These results suggested that global dissemination and local clonal expansion simultaneously occurred in Guangdong, China, and horizontally acquired resistance to first-line and last-line antimicrobials at local level, underlying emergences of extensive drug and pan-drug resistance. Our findings have increased the knowledge of global and local epidemics of Salmonella 4,[5],12:i:- in Guangdong, China, and provided a comprehensive baseline data set essential for future molecular surveillance.IMPORTANCESalmonella 4,[5],12:i:- has been regarded as the predominant pandemic serotype causing diarrheal diseases globally, while multidrug resistance (MDR) constitutes great public health concerns. This study provided a detailed and comprehensive genome-scale analysis of this important Salmonella serovar in the past decade in Guangdong, China. Our results revealed the complexity of two distinct transmission modes, namely global transmission and local expansion, circulating in Guangdong over a decade. Using phylogeography models, the origin of Salmonella 4,[5],12:i:- was predicted from two aspects, year and country, that is, Salmonella 4,[5],12:i:- emerged in 1983, and was introduced from the UK, and subsequently differentiated into the local endemic lineage circa 1991. Additionally, based on the pan-genome analysis, it was found that the gene accumulation rate in local endemic BAPS 1 lineage was higher than in other lineages, and the horizontal transmission of MDR IncHI2 plasmid associated with high resistance played a major role, which showed the potential threat to public health.
Subject(s)
Drug Resistance, Multiple, Bacterial , Salmonella Infections , Whole Genome Sequencing , China/epidemiology , Drug Resistance, Multiple, Bacterial/genetics , Humans , Salmonella Infections/microbiology , Salmonella Infections/epidemiology , Salmonella Infections/transmission , Salmonella Infections/drug therapy , Anti-Bacterial Agents/pharmacology , Genome, Bacterial/genetics , Salmonella typhimurium/drug effects , Salmonella typhimurium/genetics , Microbial Sensitivity Tests , Phylogeny , Genomics , Plasmids/geneticsABSTRACT
Salmonella infections are a serious global health concern, particularly in developing countries, and are further exacerbated by the emergence of antibiotic resistance. San-Huang-Xie-Xin-Tang (SHXXT), a traditional herbal medicine with potent anti-inflammatory properties, has recently gained attention as an alternative treatment. Our study emphasizes on the importance of precise timing in accordance with traditional Chinese medicine principles. A mouse infection model was established while different administration times of SHXXT were recorded for the body weight, clinical scores, bacterial counts in blood, and organs. Additionally, cytokine levels, fatty acids, and amino acids in the serum were also monitored. We found that administering SHXXT 1 day after Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) infection (T1 group) leads to positive outcomes. This includes restoration of body weight, improved clinical scores, and reduced bacterial counts in blood and vital organs. Interferon-gamma levels remained consistently high across all treatment groups 6 days post-infection. However, the T1 group showed exclusive suppression of serum levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß). The timing of administration significantly influenced serum fatty acid concentrations, countering Salmonella-induced disruptions, aligning with TNF-α and IL-1ß levels. SHXXT had also restored amino acid profiles disrupted by the infection, with notable effects when administered at the correct timing. Our research highlights SHXXT's potential in treating S. Typhimurium infection, emphasizing the importance of precise timing in line with traditional Chinese medicine principles for effective treatment at different disease stages.
Subject(s)
Drugs, Chinese Herbal , Salmonella typhimurium , Animals , Salmonella typhimurium/drug effects , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/pharmacology , Mice , Salmonella Infections/drug therapy , Salmonella Infections/microbiology , Cytokines/blood , Cytokines/metabolism , Female , Male , Mice, Inbred BALB CABSTRACT
The increasing antibiotic resistance poses a significant global health challenge, threatening our ability to combat infectious diseases. The phenomenon of collateral sensitivity, whereby resistance to one antibiotic is accompanied by increased sensitivity to another, offers potential avenues for novel therapeutic interventions against infections unresponsive to classical treatments. In this study, we elucidate the emergence of tobramycin (TOB)-resistant small colony variants (SCVs) due to mutations in the hemL gene, which render S. Typhimurium more susceptible to nitrofurantoin (NIT). Mechanistic studies demonstrate that the collateral sensitivity in TOB-resistant S. Typhimurium SCVs primarily stems from disruptions in haem biosynthesis. This leads to dysfunction in the electron transport chain (ETC) and redox imbalance, ultimately inducing lethal accumulation of reactive oxygen species (ROS). Additionally, the upregulation of nfsA/B expressions facilitates the conversion of NIT prodrug into its active form, promoting ROS-mediated bacterial killing and contributing to this collateral sensitivity pattern. Importantly, alternative NIT therapy demonstrates a significant reduction of bacterial load by more than 2.24-log10 cfu/g in the murine thigh infection and colitis models. Our findings corroborate the collateral sensitivity of S. Typhimurium to nitrofurans as a consequence of evolving resistance to aminoglycosides. This provides a promising approach for treating infections due to aminoglycoside-resistant strains.
Subject(s)
Anti-Bacterial Agents , Nitrofurantoin , Salmonella typhimurium , Tobramycin , Nitrofurantoin/pharmacology , Animals , Salmonella typhimurium/drug effects , Salmonella typhimurium/genetics , Tobramycin/pharmacology , Mice , Anti-Bacterial Agents/pharmacology , Microbial Sensitivity Tests , Drug Resistance, Bacterial/genetics , Mutation , Female , Reactive Oxygen Species/metabolism , Salmonella Infections/microbiology , Salmonella Infections/drug therapy , Bacterial Proteins/genetics , Bacterial Proteins/metabolismABSTRACT
BACKGROUND: Multidrug resistance Salmonellosis remains an important public health problem globally. The disease is among the leading causes of morbidity and mortality in developing countries, but there have been limited recent studies about the prevalence, antimicrobial resistance, and multidrug resistance patterns of Salmonella isolates from various clinical specimens. OBJECTIVE: Aimed to assess the prevalence, antimicrobial resistance, and multidrug resistance patterns of Salmonella isolates from clinical specimens at the University of Gondar Comprehensive Specialised Hospital, northwestern Ethiopia. METHOD: A retrospective hospital-based cross-sectional study was conducted to determine the prevalence, antimicrobial resistance, and multidrug resistance patterns of isolated from all clinical specimens at the University of Gondar Salmonella Comprehensive Specialised Hospital from June 1st, 2017 to June 3rd, 2022. A total of 26,154 data points were collected using a checklist of records of laboratory registration. Clinical specimens were collected, inoculated, and incubated for about a week with visual inspection for growth and gram staining. The isolates were grown on MacConkey agar and Xylose Lysine Deoxycholate agar. Pure colonies were identified with a conventional biochemical test, and those unidentified at the species level were further identified by the analytical profile index-20E. Then, antimicrobial susceptibility was determined by the Kirby-Bauer disc diffusion technique. The multidrug resistance Salmonella isolates was identified using the criteria set by Magiorakos. Finally, the data was cleaned and checked for completeness and then entered into SPSS version 26 for analysis. Then the results were displayed using tables and figures. RESULTS: Of the total 26,154 Salmonella suspected clinical samples, 41 (0.16%) Salmonella species were isolated. Most of the Salmonella isolates, 19 (46.3%), were in the age group of less than 18 years, followed by the age group of 19-44 years, 11 (26.8%). In this study, S. enterica subsp. arizonae accounts for the highest 21 (51%), followed by S. paratyphi A 9 (22%). Of the Salmonella isolates, S. typhi were highly resistant to ampicillin (100%), followed by tetracycline and trimethoprim-sulfamethoxazole, each accounting for 83.3%. Furthermore, S. paratyphi A was resistant to ampicillin (100%), tetracycline (88.9%), and chloramphenicol (88.9%). The overall multi-drug resistance prevalence was 22 (53.7%; 95% CI: 39.7-61). Accordingly, S. paratyphi A was 100% multidrug-resistant, followed by S. typhi (66.6%). CONCLUSION: A low prevalence of Salmonella species was observed in the past six years. Moreover, most S. typhi and S. paratyphi strains in the study area were found to be resistant to routinely recommended antibiotics like ciprofloxacin and ceftriaxone, compared to what was reported earlier. In addition, all isolates of S. paratyphi A and the majority of S. typhi were multidrug resistant. Therefore, health professionals should consider antimicrobial susceptibility tests and use antibiotics with caution for Salmonellosis management.
Subject(s)
Anti-Bacterial Agents , Drug Resistance, Multiple, Bacterial , Salmonella Infections , Salmonella , Ethiopia/epidemiology , Humans , Retrospective Studies , Salmonella/drug effects , Salmonella/isolation & purification , Prevalence , Adult , Adolescent , Young Adult , Female , Anti-Bacterial Agents/pharmacology , Cross-Sectional Studies , Male , Salmonella Infections/microbiology , Salmonella Infections/epidemiology , Salmonella Infections/drug therapy , Child , Microbial Sensitivity Tests , Middle Aged , Child, Preschool , Infant , Hospitals, SpecialABSTRACT
We report a case of septic arthritis in a 43-year-old female patient. Despite initial treatment with ceftriaxone for Nontyphoidal Salmonella based on blood and joint fluid culture results, the shoulder joint pain worsened. Suspected systemic lupus erythematosus associated synovitis did not respond to immunosuppressive therapy including methylprednisolone, hydroxychloroquine and methotrexate. Subsequent radiograph revealed a shoulder joint abscess, leading to arthroscopic joint debridement. Ceftriaxone was administered post-operatively until analgesic efficacy was attained. This case highlights the significance of accurate diagnosis and appropriate treatment for nontyphoidal Salmonella septic arthritis.
Subject(s)
Anti-Bacterial Agents , Arthritis, Infectious , Lupus Erythematosus, Systemic , Salmonella Infections , Humans , Female , Arthritis, Infectious/microbiology , Arthritis, Infectious/drug therapy , Arthritis, Infectious/diagnosis , Adult , Lupus Erythematosus, Systemic/complications , Salmonella Infections/microbiology , Salmonella Infections/diagnosis , Salmonella Infections/drug therapy , Salmonella Infections/complications , Anti-Bacterial Agents/therapeutic use , Ceftriaxone/therapeutic use , Treatment Outcome , Debridement , Shoulder Joint/microbiology , Shoulder Joint/surgery , Salmonella/isolation & purificationABSTRACT
BACKGROUND: Diarrhea caused by Salmonella and Shigella species are the leading cause of illness especially in developing countries. These infections are considered as the main public health problems in children, including Ethiopia. This study aimed to assess the prevalence, associated factors, and antimicrobial susceptibility patterns of Salmonella and Shigella species in Sheik Hassan Yabere Referral Hospital Jigjiga, Eastern Ethiopia from August 05 to November 15, 2022. METHOD: A cross-sectional study was conducted among 239 under-five children with diarrhea selected through a convenient sampling technique. A structured questionnaire was used to collect associated factors. A stool sample was collected and processed for the identification of Salmonella and Shigella species using MacConkey adar, Xylose Lysine Deoxycholate agar (Oxoid Ltd) and Biochemical tests. The antimicrobial susceptibility pattern of isolates was performed using the Kirby-Bauer disc diffusion technique. The data was entered into Epi-data version 4.6 and exported to the statistical package of social science version 22 for analysis. The association between outcome and independent variables was assessed using bivariate, multivariable, and chi-square and P-value < 0.05 was considered as statistical significance. RESULT: Overall prevalence of Salmonella and Shigella species was 6.3% (95% CI, 5.7-6.9%), of which 3.8% (95 CI, 3.2-4.4%) were Salmonella species and 2.5% (95% CI, 1.95-3%) were Shigella species. Unimproved water source (AOR = 5.08, 95% CI = 1.45, 17.25), open field (AOR = 2.3, 95% CI = 1.3, 5.03), rural residence (AOR = 1.8, 95% CI = 1.4, 7.5), Hand-washing practice (p = 0.001), and raw meat consumption (p = 0.002) were associated with occurrence of Salmonella and Shigella species. Salmonella and Shigella isolates were resistant to Ampicilin (100%). However, Salmonella isolates was sensitive to Norfloxacin (100%). About 22.2% and 16.7% of Salmonella and Shigella isolates were multi-drug resistant, respectively. CONCLUSION: Prevalence of Salmonella and Shigella species were lower than most studies done in Ethiopia. Hand-washing habit, water source type, Open field waste disposal habit, raw meat consumption and rural residence were associated with Salmonellosis and shigellosis. All isolated Salmonella were sensitive to norfloxacin. The evidence from this study underscores the need for improved water, sanitation and hygiene (WASH) system and the imperative to implement drug susceptibility tests for the treatment of Salmonella and Shigella infection.
Subject(s)
Diarrhea , Dysentery, Bacillary , Microbial Sensitivity Tests , Salmonella , Shigella , Humans , Ethiopia/epidemiology , Cross-Sectional Studies , Child, Preschool , Female , Salmonella/isolation & purification , Salmonella/drug effects , Male , Prevalence , Shigella/drug effects , Shigella/isolation & purification , Infant , Diarrhea/microbiology , Diarrhea/epidemiology , Dysentery, Bacillary/epidemiology , Dysentery, Bacillary/microbiology , Dysentery, Bacillary/drug therapy , Salmonella Infections/epidemiology , Salmonella Infections/microbiology , Salmonella Infections/drug therapy , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Risk Factors , Feces/microbiology , Drug Resistance, BacterialABSTRACT
The gut microbiota plays a significant role in the pathogenesis and remission of inflammatory bowel disease. However, conventional antibiotic therapies may alter microbial ecology and lead to dysbiosis of the gut microbiome, which greatly limits therapeutic efficacy. To address this challenge, novel nanomicelles that couple inulin with levofloxacin via disulfide bonds for the treatment of salmonellosis were developed in this study. Owing to their H2S-responsiveness, the nanomicelles can target the inflamed colon and rapidly release levofloxacin to selectively fight against enteric pathogens. Moreover, the embedded inulin can serve as prebiotic fiber to increase the amount of Bifidobacteria and Lactobacilli in mice with salmonellosis, thus maintaining the intestinal mechanical barrier and regulating the balance of the intestinal flora. Therefore, multifunctional nanomicelles had a better curative effect than pure levofloxacin on ameliorating inflammation in vivo. The pathogen-targeted glycovesicle represents a promising drug delivery platform to maximize the efficacy of antibacterial drugs for the treatment of inflammatory bowel disease.
Subject(s)
Anti-Bacterial Agents , Gastrointestinal Microbiome , Inulin , Salmonella Infections , Animals , Inulin/pharmacology , Inulin/chemistry , Mice , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Salmonella Infections/drug therapy , Salmonella Infections/microbiology , Gastrointestinal Microbiome/drug effects , Drug Delivery Systems , Levofloxacin/pharmacology , Micelles , Drug Carriers/chemistry , Nanoparticles/chemistryABSTRACT
Infections with non-typhoidal salmonella (NTS) most commonly cause localised infections such as cutaneous abscesses in humans and are a leading source of foodborne illness. Here, we present a unique case of NTS Choleraesuis in a perianal abscess in an immunocompetent patient without any comorbidities.A woman in her late 40s was diagnosed with a perianal abscess with an unknown origin of infection. The patient has undergone an incision and drainage. Her pus culture and sensitivity report yielded Salmonella enterica serotype Choleraesuis. Then, the patient recovered after treatment with intravenous antibiotics and supportive treatment.We present an unusual case of S. enterica serotype Choleraesuis, which is rarely reported as a causative agent of perianal abscess in India. This case has been reported for its rarity in India.
Subject(s)
Salmonella Infections , Salmonella enterica , Skin Diseases , Typhoid Fever , Female , Humans , Abscess/diagnosis , Salmonella Infections/complications , Salmonella Infections/diagnosis , Salmonella Infections/drug therapy , Serogroup , Anti-Bacterial Agents/therapeutic use , Skin Diseases/drug therapy , Typhoid Fever/drug therapyABSTRACT
Colistin remains one of the last-resort therapies for combating infections caused by multidrug-resistant (MDR) Enterobacterales, despite its adverse nephro- and neuro-toxic effects. This study elucidates the mechanism of action of a non-antibiotic 4-anilinoquinazoline-based compound that synergistically enhances the effectiveness of colistin against Salmonella enterica. The quinazoline sensitizes Salmonella by deactivating intrinsic, mutational, and transferable resistance mechanisms that enable Salmonella to counteract the antibiotic impact colistin, together with an induced disruption to the electrochemical balance of the bacterial membrane. The attenuation of colistin resistance via the combined treatment approach also proves efficacious against E. coli, Klebsiella, and Acinetobacter strains. The dual therapy reduces the mortality of Galleria mellonella larvae undergoing a systemic Salmonella infection when compared to individual drug treatments. Overall, our findings unveil the potential of the quinazoline-colistin combined therapy as an innovative strategy against MDR bacteria.