scholarly journals Comparison of transcriptional responses and metabolic alterations in three multidrug resistant model microorganisms, Staphylococcus aureus ATCC BAA-39, Escherichia coli ATCC BAA-196 and Acinetobacter baumannii ATCC BAA-1790, on exposure to iodine-containing nano-micelle drug FS-1

2020 ◽  
Author(s):  
Ilya S. Korotetskiy ◽  
Sergey V. Shilov ◽  
Tatyana V. Kuznetsova ◽  
Aleksandr I. Ilin ◽  
Monique Joubert ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Gene Regulation ◽  
Acinetobacter Baumannii ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Genome Sequences ◽  
Antibiotic Resistant ◽  
Reference Strains ◽  
Sublethal Concentrations

AbstractIodine is one of the oldest antimicrobial agents. Till now there have been no reports on acquiring resistance to iodine. Recent studies showed promising results on application of iodine-containing nano-micelles, FS-1, against antibiotic resistant pathogens as a supplement to antibiotic therapy. The mechanisms of the action, however, remain unclear. The aim of this study was to perform a holistic analysis and comparison of gene regulation in three phylogenetically distant multidrug resistant reference strains representing pathogens associated with nosocomial infections from the ATCC culture collection: Escherichia coli BAA-196, Staphylococcus aureus BAA-39 and Acinetobacter baumannii BAA-1790. These cultures were treated by a 5 min exposure to sublethal concentrations of the iodine-containing drug FS-1 applied in the late lagging and the mid of the logarithmic growth phases. Complete genome sequences of these strains were obtained in the previous studies. Gene regulation was studied by total RNA extraction and Ion Torrent sequencing followed by mapping the RNA reads against the reference genome sequences and statistical processing of read counts using the DESeq2 algorithm. It was found that the treatment of bacteria with FS-1 profoundly affected the expression of many genes involved in central metabolic pathways; however, alterations of the gene expression profiles were species-specific and depended on the growth phase. Disruption of respiratory electron-transfer membrane complexes, increased penetrability of bacterial cell walls, osmotic and oxidative stresses leading to DNA damaging were the major factors influencing the treated bacteria.IMPORTANCEInfections caused by antibiotic resistant bacteria threaten the public health worldwide. Combinatorial therapy when antibiotics are administrated together with supplementary drugs improving susceptibility of pathogens to the regular antibiotics is considered as a promising way to overcome this problem. An induction of antibiotic resistance reversion by the iodine-containing nano-micelle drug FS-1 has been reported recently. This drug is currently under clinical trials in Kazakhstan against multidrug resistant tuberculosis. The effects of released iodine on metabolic and regulatory processes in bacterial cells remain unexplored. The current work provides an insight into gene regulation in the antibiotic resistant nosocomial reference strains treated with iodine-containing nanoparticles. This study sheds light on unexplored bioactivities of iodine and the mechanisms of its antibacterial effect when applied in sublethal concentrations. This knowledge will aid in the future design of new drugs against antibiotic resistant infections.

scholarly journals Comparison of Transcriptional Responses and Metabolic Alterations in Three Multidrug-Resistant Model Microorganisms, Staphylococcus aureus ATCC BAA-39, Escherichia coli ATCC BAA-196, and Acinetobacter baumannii ATCC BAA-1790, on Exposure to Iodine-Containing Nano-micelle Drug FS-1

mSystems ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Ilya S. Korotetskiy ◽  
Sergey V. Shilov ◽  
Tatyana V. Kuznetsova ◽  
Aleksandr I. Ilin ◽  
Monique Joubert ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Gene Regulation ◽  
Growth Phase ◽  
Multidrug Resistant ◽  
Genome Sequences ◽  
Antibiotic Resistant ◽  
Content Type ◽  
Reference Strains ◽  
Sublethal Concentrations

ABSTRACT Iodine is one of the oldest antimicrobial agents. Until now, there have been no reports on acquiring resistance to iodine. Recent studies showed promising results on application of iodine-containing nano-micelles, FS-1, against antibiotic-resistant pathogens as a supplement to antibiotic therapy. The mechanisms of the action, however, remain unclear. The aim of this study was to perform a holistic analysis and comparison of gene regulation in three phylogenetically distant multidrug-resistant reference strains representing pathogens associated with nosocomial infections from the ATCC culture collection: Escherichia coli BAA-196, Staphylococcus aureus BAA-39, and Acinetobacter baumannii BAA-1790. These cultures were treated by a 5-min exposure to sublethal concentrations of the iodine-containing drug FS-1 applied in the late lagging phase and the middle of the logarithmic growth phase. Complete genome sequences of these strains were obtained in the previous studies. Gene regulation was studied by total RNA extraction and Ion Torrent sequencing followed by mapping the RNA reads against the reference genome sequences and statistical processing of read counts using the DESeq2 algorithm. It was found that the treatment of bacteria with FS-1 profoundly affected the expression of many genes involved in the central metabolic pathways; however, alterations of the gene expression profiles were species specific and depended on the growth phase. Disruption of respiratory electron transfer membrane complexes, increased penetrability of bacterial cell walls, and osmotic and oxidative stresses leading to DNA damage were the major factors influencing the treated bacteria. IMPORTANCE Infections caused by antibiotic-resistant bacteria threaten public health worldwide. Combinatorial therapy in which antibiotics are administered together with supplementary drugs improving susceptibility of pathogens to the regular antibiotics is considered a promising way to overcome this problem. An induction of antibiotic resistance reversion by the iodine-containing nano-micelle drug FS-1 has been reported recently. This drug is currently under clinical trials in Kazakhstan against multidrug-resistant tuberculosis. The effects of released iodine on metabolic and regulatory processes in bacterial cells remain unexplored. The current work provides an insight into gene regulation in the antibiotic-resistant nosocomial reference strains treated with iodine-containing nanoparticles. This study sheds light on unexplored bioactivities of iodine and the mechanisms of its antibacterial effect when applied in sublethal concentrations. This knowledge will aid in the future design of new drugs against antibiotic-resistant infections.

scholarly journals Time-Resolved Transcriptional Profiling of Epithelial Cells Infected by Intracellular Acinetobacter baumannii

2021 ◽  
Vol 9 (2) ◽  
pp. 354
Author(s):  
Nuria Crua Asensio ◽  
Javier Macho Rendón ◽  
Marc Torrent Burgas
Keyword(s):  
Acinetobacter Baumannii ◽  
Transcriptional Profiling ◽  
Multidrug Resistant ◽  
Host Cells ◽  
Resistant Bacteria ◽  
Multidrug Resistant Bacteria ◽  
Time Resolved ◽  
Antibiotic Resistant ◽  
Common Features ◽  
Profile Changes

The rise in the number of antibiotic-resistant bacteria has become a serious threat to health, making it important to identify, characterize and optimize new molecules to help us to overcome the infections they cause. It is well known that Acinetobacter baumannii has a significant capacity to evade the actions of antibacterial drugs, leading to its emergence as one of the bacteria responsible for hospital and community-acquired infections. Nonetheless, how this pathogen infects and survives inside the host cell is unclear. In this study, we analyze the time-resolved transcriptional profile changes observed in human epithelial HeLa cells after infection by A. baumannii, demonstrating how it survives in host cells and starts to replicate 4 h post infection. These findings were achieved by sequencing RNA to obtain a set of Differentially Expressed Genes (DEGs) to understand how bacteria alter the host cells’ environment for their own benefit. We also determine common features observed in this set of genes and identify the protein–protein networks that reveal highly-interacted proteins. The combination of these findings paves the way for the discovery of new antimicrobial candidates for the treatment of multidrug-resistant bacteria.

scholarly journals Retail Chicken Carcasses as a Reservoir of Antimicrobial- Resistant Escherichia coli

2020 ◽  
Author(s):  
Nahla Omer Eltai ◽  
Hadi M. Yassine ◽  
Sara H. Al-Hadidi ◽  
Tahra ElObied ◽  
Asmaa A. Al Thani ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Resistance ◽  
Growth Promotion ◽  
Multidrug Resistant ◽  
Chicken Meat ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
E Coli ◽  
Inappropriate Use ◽  
Esbl Producers

The dissemination of antimicrobial resistance (AMR) bacteria has been associated with the inappropriate use of antibiotics in both humans and animals and with the consumption of food contaminated with resistant bacteria. In particular, the use of antibiotics as prophylactic and growth promotion purposes in food-producing animals has rendered many of the antibiotics ineffective. The increased global prevalence of AMR poses a significant threat to the safety of the world’s food supply. Objectives: This study aims at determining the prevalence of antibiotic-resistant Escherichia coli (E. coli) isolated from local and imported retail chicken meat in Qatar. Methodology: A total of 270 whole chicken carcasses were obtained from three different hypermarket stores in Qatar. A total of 216 E. coli were isolated and subjected to antibiotic susceptibility testing against 18 relevant antibiotics using disc diffusion and micro- dilution methods. Furthermore, extended-spectrum β-lactamase (ESBL) production was determined via a double-disc synergetic test. Isolates harboring colistin resistance were confirmed using multiplex-PCR and DNA sequencing. Results: Nearly 89% (192/216) of the isolates were resistant to at least one antibiotics. In general, isolates showed relatively higher resistance to sulfamethoxazole (62%), tetracycline (59.7%), ampicillin and trimethoprim (52.3%), ciprofloxacin (47.7%), cephalothin, and colistin (31.9%). On the other hand, less resistance was recorded against amoxicillin/clavulanic acid (6%), ceftriaxone (5.1%), nitrofurantoin (4.2%) and piperacillin/tazobactam (4.2%), cefepime (2.3%), meropenem (1.4%), ertapenem (0.9%), and amikacin (0.9%). Nine isolates (4.2%) were ESBL producers. Furthermore, 63.4% were multidrug-resistant (MDR). The percentage of MDR, ESBL producers, and colistin-resistant isolates was significantly higher among local isolates compared to imported chicken samples. Conclusion: We reported a remarkably high percentage of the antibiotic-resistant E. coli in chicken meat sold at retail in Qatar. The high percentage of MDR and colistin isolates is troublesome to the food safety of raw chicken meat and the potential of antibiotic resistance spread to public health. Our findings support the need for the implementation of one health approach to address the spread of antimicrobial resistance and the need for a collaborative solution.

scholarly journals Hypochlorite-Activated Fluorescence Emission and Antibacterial Activities of Imidazole Derivatives for Biological Applications

2021 ◽  
Vol 9 ◽  
Author(s):  
Thanh Chung Pham ◽  
Van-Nghia Nguyen ◽  
Yeonghwan Choi ◽  
Dongwon Kim ◽  
Ok-Sang Jung ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Stokes Shift ◽  
Fluorescence Emission ◽  
Antibacterial Activities ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Fluorogenic Probe ◽  
High Fluorescence

The ability to detect hypochlorite (HOCl/ClO−) in vivo is of great importance to identify and visualize infection. Here, we report the use of imidazoline-2-thione (R1SR2) probes, which act to both sense ClO− and kill bacteria. The N2C=S moieties can recognize ClO− among various typical reactive oxygen species (ROS) and turn into imidazolium moieties (R1IR2) via desulfurization. This was observed through UV–vis absorption and fluorescence emission spectroscopy, with a high fluorescence emission quantum yield (ՓF = 43–99%) and large Stokes shift (∆v∼115 nm). Furthermore, the DIM probe, which was prepared by treating the DSM probe with ClO−, also displayed antibacterial efficacy toward not only Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) but also methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum ß-lactamase–producing Escherichia coli (ESBL-EC), that is, antibiotic-resistant bacteria. These results suggest that the DSM probe has great potential to carry out the dual roles of a fluorogenic probe and killer of bacteria.

scholarly journals High Colonization Rate and Heterogeneity of ESBL- and Carbapenemase-Producing Enterobacteriaceae Isolated from Gull Feces in Lisbon, Portugal

2020 ◽  
Vol 8 (10) ◽  
pp. 1487
Author(s):  
Marta Aires-de-Sousa ◽  
Claudine Fournier ◽  
Elizeth Lopes ◽  
Hermínia de Lencastre ◽  
Patrice Nordmann ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Bacterial Species ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Multidrug Resistant Bacteria ◽  
Vancomycin Resistant Enterococci ◽  
Vancomycin Resistant ◽  
Encoding Genes

In order to evaluate whether seagulls living on the Lisbon coastline, Portugal, might be colonized and consequently represent potential spreaders of multidrug-resistant bacteria, a total of 88 gull fecal samples were screened for detection of extended-spectrum β-lactamase (ESBL)- or carbapenemase-producing Enterobacteriaceae for methicillin-resistant Staphylococcus aureus (MRSA) and for vancomycin-resistant Enterococci (VRE). A large proportion of samples yielded carbapenemase- or ESBL-producing Enterobacteriaceae (16% and 55%, respectively), while only two MRSA and two VRE were detected. Mating-out assays followed by PCR and whole-plasmid sequencing allowed to identify carbapenemase and ESBL encoding genes. Among 24 carbapenemase-producing isolates, there were mainly Klebsiella pneumoniae (50%) and Escherichia coli (33%). OXA-181 was the most common carbapenemase identified (54%), followed by OXA-48 (25%) and KPC-2 (17%). Ten different ESBLs were found among 62 ESBL-producing isolates, mainly being CTX-M-type enzymes (87%). Co-occurrence in single samples of multiple ESBL- and carbapenemase producers belonging to different bacterial species was observed in some cases. Seagulls constitute an important source for spreading multidrug-resistant bacteria in the environment and their gut microbiota a formidable microenvironment for transfer of resistance genes within bacterial species.

scholarly journals Design, Overproduction and Purification of the Chimeric Phage Lysin MLTphg Fighting against Staphylococcus aureus

Processes ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 1587
Author(s):  
Feng Wang ◽  
Xiaohang Liu ◽  
Zhengyu Deng ◽  
Yao Zhang ◽  
Xinyu Ji ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
E Coli ◽  
Conventional Antibiotics ◽  
Phage Lysin ◽  
Shed Light

With the increasing spread of multidrug-resistant bacterial pathogens, it is of great importance to develop alternatives to conventional antibiotics. Here, we report the generation of a chimeric phage lysin, MLTphg, which was assembled by joining the lysins derived from Meiothermus bacteriophage MMP7 and Thermus bacteriophage TSP4 with a flexible linker via chimeolysin engineering. As a potential antimicrobial agent, MLTphg can be obtained by overproduction in Escherichia coli BL21(DE3) cells and the following Ni-affinity chromatography. Finally, we recovered about 40 ± 1.9 mg of MLTphg from 1 L of the host E. coli BL21(DE3) culture. The purified MLTphg showed peak activity against Staphylococcus aureus ATCC6538 between 35 and 40 °C, and maintained approximately 44.5 ± 2.1% activity at room temperature (25 °C). Moreover, as a produced chimera, it exhibited considerably improved bactericidal activity against Staphylococcus aureus (2.9 ± 0.1 log10 reduction was observed upon 40 nM MLTphg treatment at 37 °C for 30 min) and also a group of antibiotic-resistant bacteria compared to its parental lysins, TSPphg and MMPphg. In the current age of growing antibiotic resistance, our results provide an engineering basis for developing phage lysins as novel antimicrobial agents and shed light on bacteriophage-based strategies to tackle bacterial infections.

scholarly journals Acquisition of a High Diversity of Bacteria during the Hajj Pilgrimage, Including Acinetobacter baumannii withblaOXA-72and Escherichia coli withblaNDM-5Carbapenemase Genes

2016 ◽  
Vol 60 (10) ◽  
pp. 5942-5948 ◽  
Author(s):  
Thongpan Leangapichart ◽  
Philippe Gautret ◽  
Karolina Griffiths ◽  
Khadidja Belhouchat ◽  
Ziad Memish ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Acinetobacter Baumannii ◽  
Rectal Swab ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Pharyngeal Swab ◽  
Content Type ◽  
Carbapenemase Gene ◽  
Before And After ◽  
Pcr Targeting

ABSTRACTPilgrims returning from the Hajj (pilgrimage to Mecca) can be carriers of multidrug-resistant bacteria (MDR). Pharyngeal and rectal swab samples were collected from 98 pilgrims before and after they traveled to the Hajj in 2014 to investigate the acquisition of MDR bacteria. The bacterial diversity in pharyngeal swab samples was assessed by culture with selective media. There was a significantly higher diversity of bacteria in samples collected after the return from the Hajj than in those collected before (P= 0.0008). Surprisingly,Acinetobacter baumanniistrains were isolated from 16 pharyngeal swab samples (1 sample taken during the Hajj and 15 samples taken upon return) and 26 post-Hajj rectal swab samples, while none were isolated from samples taken before the Hajj. Testing of all samples by real-time PCR targetingblaOXA-51gave positive results for only 1% of samples taken during the Hajj, 21/90 (23.3%) pharyngeal swab samples taken post-Hajj, and 35/90 (38.9%) rectal swab samples taken post-Hajj. One strain ofA. baumanniiisolated from the pharynx was resistant to imipenem and harbored ablaOXA-72carbapenemase gene. Multilocus sequence typing analysis of 43A. baumanniiisolates revealed a huge diversity of 35 sequence types (STs), among which 18 were novel STs reported for the first time in this study. Moreover, we also found oneEscherichia coliisolate, collected from a rectal swab sample from a pilgrim taken after the Hajj, which harboredblaNDM-5,blaCTX-M-15,blaTEM-1, andaadA2(ST2659 and ST181). In conclusion, pilgrims are at a potential risk of acquiring and transmitting MDRAcinetobacterspp. and carbapenemase-producing Gram-negative bacteria during the Hajj season.

scholarly journals Investigation of the environmental presence of multidrug-resistant bacteria at small animal hospitals in Hungary

2021 ◽  
Author(s):  
Ádám Kerek ◽  
Ágnes Sterczer ◽  
Zoltán Somogyi ◽  
Dóra Kovács ◽  
Ákos Jerzsele
Keyword(s):  
Staphylococcus Aureus ◽  
Susceptibility Testing ◽  
Small Animal ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Multidrug Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Hygiene Measures ◽  
High Prevalence ◽  
Vancomycin Resistant

AbstractMultidrug-resistant bacteria can cause severe nosocomial infections in both human and veterinary clinics. The aim of this study was to investigate the presence and antibiotic susceptibility of Enterococcus, Staphylococcus and Pseudomonas strains at four small animal clinics of Hungary in 2018, as these bacteria can reliably represent the level of antimicrobial resistance in the investigated environment. A total of 177 Staphylococcus colonies were found, including 22 Staphylococcus pseudintermedius and 13 Staphylococcus aureus. As regards enterococci, 9 Enterococcus faecium, 2 E. faecalis and further 286 Enterococcus strains were isolated. The number of Pseudomonas aeruginosa isolates (n = 34) was considered too low for relevant susceptibility testing. Among staphylococci, the highest resistance was found to sulphamethoxazole (82.9%), penicillin (65.7%) and erythromycin (54.3%), while in the case of enterococci, resistance to norfloxacin and rifampicin was the most common, with 25.5% of the strains being resistant to both antibiotics. Ten methicillin-resistant S. pseudintermedius (MRSP) and six vancomycin-resistant Enterococcus (VRE) strains could be identified. Only 5.7% of the Staphylococcus isolates were susceptible to all tested agents, while this ratio was 36.2% among enterococci. The results of this study have revealed a high prevalence of antibiotic-resistant bacteria in Hungarian small animal clinics, which highlights the importance of regular disinfection processes and stringent hygiene measures in veterinary clinics.

scholarly journals Antimicrobial activity of a repurposed harmine-derived compound on extensively drug-resistant Acinetobacter baumannii clinical isolates

2021 ◽  
Author(s):  
Anke Breine ◽  
Megane Van Gysel ◽  
Mathias Elsocht ◽  
Clemence Whiteway ◽  
Chantal Philippe ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Reference Strain ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Antibiotic Resistant ◽  
Carbapenem Resistant ◽  
Extensively Drug Resistant ◽  
Resistant Strains ◽  
High Degree

Synopsis Objectives: The spread of antibiotic resistant bacteria is an important threat for human healthcare. Acinetobacter baumannii bacteria impose one of the major issues, as multidrug- to pandrug-resistant strains have been found, rendering some infections untreatable. In addition, A. baumannii is a champion in surviving in harsh environments, being capable of resisting to disinfectants and to persist prolonged periods of desiccation. Due to the high degree of variability found in A. baumannii isolates, the search for new antibacterials is challenging. Here, we screened a compound library to identify compounds active against recent isolates of A. baumannii bacteria. Methods: A repurposing drug screen was undertaken to identify A. baumannii growth inhibitors. One hit was further characterized by determining its IC50 and testing its activity on 43 recent clinical A. baumannii isolates, amongst which 40 are extensively drug- and carbapenem-resistant strains. Results: The repurposing screen led to the identification of a harmine-derived compound, called HDC1, which proved to have bactericidal activity on the multidrug-resistant AB5075-VUB reference strain with an IC50 of 48.23 [mu]M. In addition, HDC1 impairs growth of all 43 recent clinical A. baumannii isolates. Conclusions: We identified a compound with inhibitory activity on all tested, extensively drug-resistant clinical A. baumannii isolates.

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