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PloS One 2024Cholangiocarcinoma (CCA) is an aggressive cancer originating from bile duct epithelium, particularly prevalent in Asian countries with liver fluke infections. Current...
Cholangiocarcinoma (CCA) is an aggressive cancer originating from bile duct epithelium, particularly prevalent in Asian countries with liver fluke infections. Current chemotherapy for CCA often fails due to drug resistance, necessitating novel anticancer agents. This study investigates the potential of 5'-deoxy-5'-methylthioadenosine (MTA), a naturally occurring nucleoside, against CCA. While MTA has shown promise against various cancers, its effects on CCA remain unexplored. We evaluated MTA's anticancer activity in CCA cell lines and drug-resistant sub-lines, assessing cell viability, migration, invasion, and apoptosis. The potential anticancer mechanisms of MTA were explored through proteomic analysis using LC-MS/MS and bioinformatic analysis. The results show a dose-dependent reduction in CCA cell viability, with enhanced effects on cancer cells compared to normal cells. Moreover, MTA inhibits growth, induces apoptosis, and suppresses cell migration and invasion. Additionally, MTA enhanced the anticancer effects of gemcitabine on drug-resistant CCA cells. Proteomics revealed the down-regulation of multiple proteins by MTA, affecting various molecular functions, biological processes, and cellular components. Network analysis highlighted MTA's role in inhibiting proteins related to mitochondrial function and energy derivation, crucial for cell growth and survival. Additionally, MTA suppressed proteins involved in cell morphology and cytoskeleton organization, important for cancer cell motility and metastasis. Six candidate genes, including ZNF860, KLC1, GRAMD1C, MAMSTR, TANC1, and TTC13, were selected from the top 10 most down-regulated proteins identified in the proteomics results and were subsequently verified through RT-qPCR. Further, KLC1 protein suppression by MTA treatment was confirmed through Western blotting. Additionally, based on TCGA data, KLC1 mRNA was found to be upregulated in the tissue of CCA patients compared to that of normal adjacent tissues. In summary, MTA shows promising anticancer potential against CCA by inhibiting growth, inducing apoptosis, and suppressing migration and invasion, while enhancing gemcitabine's effects. Proteomic analysis elucidates possible molecular mechanisms underlying MTA's anticancer activity, laying the groundwork for future research and development of MTA as a treatment for advanced CCA.
Topics: Cholangiocarcinoma; Humans; Proteomics; Cell Line, Tumor; Deoxyadenosines; Bile Duct Neoplasms; Apoptosis; Cell Movement; Thionucleosides; Antineoplastic Agents; Gemcitabine; Deoxycytidine; Cell Survival; Cell Proliferation; Drug Resistance, Neoplasm
PubMed: 38923999
DOI: 10.1371/journal.pone.0306060 -
Revista Brasileira de Parasitologia... 2024Ticks are parasitic arthropods that cause significant economic losses to livestock production worldwide. Although Rhipicephalus (Boophilus) microplus, the cattle tick,... (Review)
Review
Ticks are parasitic arthropods that cause significant economic losses to livestock production worldwide. Although Rhipicephalus (Boophilus) microplus, the cattle tick, occurs throughout the Brazilian territory, there is no official program to control this tick, which is the vector of tick fever pathogens. We address the situation of R. (B.) microplus resistance to synthetic acaricides in Brazil, including cattle tick management; the status of tick resistance per Brazilian state; the history of resistance occurrence of different acaricides; multiple resistance occurrence; and the main strategies for integrated tick management. Tick control in Brazil is characterized by management errors. Local laboratories affiliated with federal and state research institutions and universities employ the Adult Immersion Test as a primary diagnostic method to assess acaricide resistance to topically applied drugs. Only three states (Acre, Amapá, and Amazonas) have no reports on resistant populations. Misinformation on tick control strategies, misuse of available products for tick control, no adoption of Integrated Parasite Management (IPM) practices, low technical support to producers, and the high-speed emergence of acaricide-resistant tick populations are the main problems. We also propose a list of needs and priorities for cattle tick control regarding communication, research, and policies.
Topics: Animals; Rhipicephalus; Brazil; Tick Control; Acaricides; Cattle; Tick Infestations; Cattle Diseases; Forecasting; Drug Resistance
PubMed: 38922203
DOI: 10.1590/S1984-29612024026 -
Toxins Jun 2024Extensively drug-resistant infections are emerging as a significant threat associated with adverse patient outcomes. Due to this organism's inherent properties of...
Extensively drug-resistant infections are emerging as a significant threat associated with adverse patient outcomes. Due to this organism's inherent properties of developing antibiotic resistance, we sought to investigate alternative strategies such as identifying "high value" antigens for immunotherapy-based purposes. Through extensive database mining, we discovered that numerous Gram-negative bacterial (GNB) genomes, many of which are known multidrug-resistant (MDR) pathogens, including , horizontally acquired the evolutionarily conserved gene encoding Zonula occludens toxin (Zot) with a substantial degree of homology. The toxin's genomic footprint among so many different GNB stresses its evolutionary importance. By employing in silico techniques such as proteomic-based phylogenetic tracing, in conjunction with comparative structural modeling, we discovered a highly conserved intermembrane associated stretch of 70 amino acids shared among all the GNB strains analyzed. The characterization of our newly identified antigen reveals it to be a "high value" vaccine candidate specific for . This newly identified antigen harbors multiple non-overlapping B- and T-cell epitopes exhibiting very high binding affinities and can adopt identical tertiary structures among the least genetically homologous strains. Taken together, using proteomic-driven reverse vaccinology techniques, we identified multiple "high value" vaccine candidates capable of eliciting a polarized immune response against all the genetic variants tested.
Topics: Pseudomonas aeruginosa; Phylogeny; Pseudomonas Infections; Humans; Epitopes, T-Lymphocyte; Pseudomonas Vaccines; Epitopes, B-Lymphocyte
PubMed: 38922165
DOI: 10.3390/toxins16060271 -
Pathogens (Basel, Switzerland) Jun 2024is a concerning pathogen, responsible for hospital-associated outbreaks. Multi drug resistant (MDR) strains are especially hard to treat. We conducted whole-genome...
Complete Genome Sequence of a Strain Carrying Novel Variant , Cross-Resistant to Ceftazidime/Avibactam and Cefiderocol, but Susceptible to Carbapenems, Isolated in Italy, 2023.
BACKGROUND
is a concerning pathogen, responsible for hospital-associated outbreaks. Multi drug resistant (MDR) strains are especially hard to treat. We conducted whole-genome sequencing on a MDR strain in order to identify genomic features potentially linked to its phenotype.
METHODS
DNA sequencing was performed on the Illumina iSeq 100 platform. Genome assembly was carried out with SPAdes. The genome was annotated with RASTtk. Typing was performed with MLST and Kaptive. Antibiotic resistance genes were detected with AMRFinderPlus and Abricate, and further verified with BLAST.
RESULTS
The strain exhibited resistance to ceftazidime/avibactam and cefiderocol, but remained susceptible to carbapenems. The strain belonged to sequence type ST101, serotype O1:K17. The analysis of antibiotic resistance genes indicated that the strain carried a novel KPC variant, designated as KPC-203, featuring a EL deletion at amino acid position 166-167, within the Ω-loop, and a nine-amino-acid insertion (LAVYTRAPM) at position 259. Sequence alterations were found in porin genes and . Unlike molecular testing, which was able to detect the KPC-203 variant, all phenotypic carbapenemase detection methods achieved negative results.
CONCLUSIONS
KPC-203, a novel KPC variant, showed a sequence modification in a cephalosporin resistance-associated hotspot. Interestingly, such alterations typically correlate with the restoration of carbapenem susceptibility. We hypothesize that KPC-203 likely led to resistance to ceftazidime/avibactam and cefiderocol, while maintaining susceptibility to carbapenems.
PubMed: 38921804
DOI: 10.3390/pathogens13060507 -
Marine Drugs Jun 2024Three new cyclic lipopeptides, olenamidonins A-C (-), in addition to two previously reported metabolites ( and ), were accumulated in the Δ deletion mutant of...
Three new cyclic lipopeptides, olenamidonins A-C (-), in addition to two previously reported metabolites ( and ), were accumulated in the Δ deletion mutant of deepsea-derived SCSIO 1071. The structures of these cyclic lipopeptides were determined by a combination of spectroscopic methods and circular dichroism (CD) measurement. The antibacterial assay results showed that compounds displayed different degrees of growth inhibition against multidrug-resistant (MDR) bacterial strains CCARM 5172 and CCARM 5203 with minimum inhibitory concentrations (MICs) of 1.56-6.25 μg/mL.
Topics: Streptomyces; Lipopeptides; Microbial Sensitivity Tests; Anti-Bacterial Agents; Enterococcus faecalis; Peptides, Cyclic; Enterococcus faecium; Drug Resistance, Multiple, Bacterial; Bacterial Proteins
PubMed: 38921573
DOI: 10.3390/md22060262 -
MBio Jun 2024This study examined the diversity and persistence of in the surface waters of agricultural regions of Brazil, Chile, and Mexico. Research groups (three in 2019-2020 and...
This study examined the diversity and persistence of in the surface waters of agricultural regions of Brazil, Chile, and Mexico. Research groups (three in 2019-2020 and five in 2021-2022) conducted a long-term survey of surface water across 5-8 months annually ( = 30 monthly). On-site, each team filtered 10-L water samples with modified Moore Swabs to capture which were then isolated and identified using conventional microbiological techniques. isolates were sequenced on Illumina platforms. was present in 1,493/3,291 water samples (45.8%), with varying isolation rates across countries and years. Newport, Infantis, and Typhimurium were the most frequent among the 128 different serovars. Notably, 22 serovars were found in all three countries, representing almost half of the 1,911 different isolates collected. The resistome comprised 72 antimicrobial resistance (AMR) genes and six point mutations in three genes. At least one AMR determinant was observed in 33.8% (646/1,911) of the isolates, of which 47.4% (306/646) were potentially multidrug resistant. Phylogeny based on core genome multilocus sequence typing (cgMLST) showed that most isolates clustered according to sequence type and country of origin. Only 14 cgMLST multi-country clusters were detected among the 275 clusters. However, further analysis confirmed that close genetic relatedness occurred mostly among isolates from the same country, with three exceptions. Interestingly, isolates closely related phylogenetically were recovered over multiple years within the same country, indicating the persistence of certain in those areas. In conclusion, surface waters in these regions are consistently contaminated with diverse , including strains that persist over time.IMPORTANCE is a leading foodborne pathogen responsible for millions of illnesses, hospitalizations, and deaths annually. Although -contaminated water has now been recognized as an important contamination source in the agrifood chain, there is a lack of knowledge on the global occurrence and diversity of in surface water. Moreover, there has been insufficient research on in surface waters from Latin American countries that are major producers and exporters of agricultural products. Incorporating genetic profiling of isolates from underrepresented regions, such as Latin America, enhances our understanding of the pathogen's ecology, evolution, antimicrobial resistance, and pathogenicity. Moreover, leveraging genomic data derived from pathogens isolated from diverse geographical areas is critical for assessing the potential public health risk posed by the pathogen and expediting investigations of foodborne outbreaks. Ultimately, global efforts contribute significantly to reducing the incidence of foodborne infections.
PubMed: 38920393
DOI: 10.1128/mbio.00777-24 -
AIMS Microbiology 2024Multidrug-resistant tuberculosis (TB) (MDR-TB), or TB that is simultaneously resistant to both isoniazid (INH) and rifampicin (RIF), is a barrier to successful TB...
Multidrug-resistant tuberculosis (TB) (MDR-TB), or TB that is simultaneously resistant to both isoniazid (INH) and rifampicin (RIF), is a barrier to successful TB control and treatment. Stratified data on MDR-TB, particularly in the high-burden western Kenya region, remain unknown. This data is important to monitor the efficacy of TB control and treatment efforts. Herein, we determined the molecular epidemiology of drug-resistant TB and associated risk factors in western Kenya. This was a non-experimental, population-based, cross-sectional study conducted between January and August 2018. Morning sputum samples of individuals suspected of pulmonary TB were collected, processed, and screened for (Mtb) and drug resistance using line probe assay (LPA) and growth indicator tubes (MGIT) culture. MGIT-positive samples were cultured on brain heart infusion (BHII) agar media, and the presence of Mtb was validated using Immunochromatographic assay (ICA). Drug sensitivity was performed on MGIT and ICA-positive but BHI-negative samples. Statistical significance was set at < 0.05. Of the 622 Mtb isolates, 536 (86.2%) were susceptible to RIF and INH. The rest, 86 (13.83%), were resistant to either drugs or both. A two-sample proportional equality test revealed that the MDR-TB prevalence in western Kenya (5%) did not vary significantly from the global MDR-TB estimate (3.9%) (P = 0.196). Men comprised the majority of susceptible and resistant TB (75.9% and 77.4%%, respectively). Also, compared with healthy individuals, the prevalence of HIV was significantly higher in MDR-TB patients (35.9% vs 5.6%). Finally, TB prevalence was highest in individuals aged 25-44 years, who accounted for 58.4% of the total TB cases. Evidently, the prevalence of MDRTB in western Kenya is high. Particular attention should be paid to men, young adults, and those with HIV, who bear the greatest burden of resistant TB. Overall, there is a need to refine TB control and treatment programs in the region to yield better outcomes.
PubMed: 38919722
DOI: 10.3934/microbiol.2024014 -
Journal of Anaesthesiology, Clinical... 2024Ventilator-associated pneumonia (VAP) is a nosocomial infection associated with high morbidity and mortality. This study was undertaken to monitor the trend of the...
Antimicrobial resistance pattern in aerobic bacteria isolated from endotracheal aspirate in ventilator-associated pneumonia: Ten years observation from a tertiary care hospital.
BACKGROUND AND AIMS
Ventilator-associated pneumonia (VAP) is a nosocomial infection associated with high morbidity and mortality. This study was undertaken to monitor the trend of the demographical details, comorbid conditions, bacterial etiological agents, and their antibiogram causing VAP in adults in the year 2008, 2013 and 2018.
MATERIAL AND METHODS
A retrospective study conducted at the Department of Microbiology, Hospital Infection control and Quality Control at a tertiary care teaching hospital. All the adult patients with more than 48 h of the mechanical ventilator with endotracheal intubation with Clinical Pulmonary infection Score >6 with suspicion of VAP were included in the study at a difference of 5 years, i.e., 2008, 2013, and 2018.
RESULTS
A total of 338 patients were included in the study, of which males accounted for more than two-third of the patients studied. Nearly 45% of the patients belonged to geriatric (>60 years) age group. The most common comorbid conditions were chronic obstructive pulmonary disease, hypertension and diabetes mellitus. Among the gram-negative isolates, , species, and were the most common. There is an emergence of resistance to most commonly administered antimicrobial agents like aminoglycosides, levofloxacin, piperacillin/tazobactum, and carbapenems during the study period.
CONCLUSION
This is a ten-year study on the antibiotic resistance pattern of organisms causing VAP. As far as the authors are aware, this is the first study addressing the pattern of change in drug resistance in the organisms causing VAP over a decade. The emergence of multi-drug resistant (MDR) MDR pathogens, especially in intensive care unit (ICU), is a great concern for the intensivist and infection control physicians. Preventive measures need to be undertaken to control the spread of these pathogens to the patients in the ICU.
PubMed: 38919443
DOI: 10.4103/joacp.joacp_410_22 -
World Journal of Surgical Oncology Jun 2024This study aimed to evaluate the oncological and reproductive outcomes of fertility-preserving re-treatment in progestin-resistant endometrial carcinoma (EC) and...
OBJECTIVE
This study aimed to evaluate the oncological and reproductive outcomes of fertility-preserving re-treatment in progestin-resistant endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) women who desire to maintain their fertility.
METHODS
Our study included 61 progestin-resistant EC/AEH patients. These patients underwent treatment with gonadotropin-releasing hormone agonist (GnRHa) solely or a combination of GnRHa with levonorgestrel-releasing intrauterine system (LNG-IUD) or aromatase inhibitor (AI). Histological evaluations were performed every 3-4 months. Upon achieving complete remission (CR), we recommended maintenance treatments including LNG-IUD, cyclical oral contraceptives, or low-dose cyclic progestin until they began attempting conception. Regular follow-up was conducted for all patients. The chi-square method was utilized to compare oncological and fertility outcomes, while the Cox proportional hazards regression analysis helped identify risk factors for CR, recurrence, and pregnancy.
RESULTS
Overall, 55 (90.2%) patients achieved CR, including 90.9% of AEH patients and 89.7% of EC patients. The median re-treatment time was 6 months (ranging from 3 to 12 months). The CR rate for GnRHa alone, GnRHa + LNG-IUD and GnRHa + AI were 80.0%, 91.7% and 93.3%, respectively. After a median follow-up period of 36 months (ranging from 3 to 96 months), 19 women (34.5%) experienced recurrence, 40.0% in AEH and 31.4% in EC patients, with the median recurrence time of 23 months (ranging from 6 to 77 months). Among the patients who achieved CR, 39 expressed a desire to conceive, 20 (51.3%) became pregnant, 11 (28.2%) had successfully deliveries, 1 (5.1%) was still pregnant, while 8 (20.5%) suffered miscarriages.
CONCLUSION
GnRHa-based fertility-sparing treatment exhibited promising oncological and reproductive outcomes for progestin-resistant patients. Future larger multi-institutional studies are necessary to confirm these findings.
Topics: Humans; Female; Endometrial Neoplasms; Adult; Retrospective Studies; Fertility Preservation; Endometrial Hyperplasia; Progestins; Follow-Up Studies; Pregnancy; Drug Resistance, Neoplasm; Gonadotropin-Releasing Hormone; Levonorgestrel; Middle Aged; Prognosis; Intrauterine Devices, Medicated; Neoplasm Recurrence, Local; Pregnancy Rate; Aromatase Inhibitors; Antineoplastic Agents, Hormonal
PubMed: 38918837
DOI: 10.1186/s12957-024-03439-w -
BMC Veterinary Research Jun 2024Acinetobacter lwoffii (A. lwoffii) is a Gram-negative bacteria common in the environment, and it is the normal flora in human respiratory and digestive tracts. The...
BACKGROUND
Acinetobacter lwoffii (A. lwoffii) is a Gram-negative bacteria common in the environment, and it is the normal flora in human respiratory and digestive tracts. The bacteria is a zoonotic and opportunistic pathogen that causes various infections, including nosocomial infections. The aim of this study was to identify A. lwoffii strains isolated from bovine milk with subclinical mastitis in China and get a better understanding of its antimicrobial susceptibility and resistance profile. This is the first study to analyze the drug resistance spectrum and corresponding mechanisms of A. lwoffii isolated in raw milk.
RESULTS
Four A. lwoffii strains were isolated by PCR method. Genetic evolution analysis using the neighbor-joining method showed that the four strains had a high homology with Acinetobacter lwoffii. The strains were resistant to several antibiotics and carried 17 drug-resistance genes across them. Specifically, among 23 antibiotics, the strains were completely susceptible to 6 antibiotics, including doxycycline, erythromycin, polymyxin, clindamycin, imipenem, and meropenem. In addition, the strains showed variable resistance patterns. A total of 17 resistance genes, including plasmid-mediated resistance genes, were detected across the four strains. These genes mediated resistance to 5 classes of antimicrobials, including beta-lactam, aminoglycosides, fluoroquinolones, tetracycline, sulfonamides, and chloramphenicol.
CONCLUSION
These findings indicated that multi-drug resistant Acinetobacter lwoffii strains exist in raw milk of bovine with subclinical mastitis. Acinetobacter lwoffii are widespread in natural environmental samples, including water, soil, bathtub, soap box, skin, pharynx, conjunctiva, saliva, gastrointestinal tract, and vaginal secretions. The strains carry resistance genes in mobile genetic elements to enhance the spread of these genes. Therefore, more attention should be paid to epidemiological surveillance and drug resistant A. lwoffii.
Topics: Animals; Cattle; Mastitis, Bovine; Female; Acinetobacter; Milk; China; Anti-Bacterial Agents; Microbial Sensitivity Tests; Acinetobacter Infections; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial
PubMed: 38918815
DOI: 10.1186/s12917-024-04119-3