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 Analysis of the Resistome of a Multidrug-Resistant NDM-1-Producing Escherichia coli Strain by High-Throughput Genome Sequencing

2011 ◽  
Vol 55 (9) ◽  
pp. 4224-4229 ◽  
Author(s):  
Laurent Poirel ◽  
Rémy A. Bonnin ◽  
Patrice Nordmann
Keyword(s):  
Escherichia Coli ◽  
Genome Sequencing ◽  
High Throughput ◽  
Multidrug Resistant ◽  
Replicase Gene ◽  
Content Type ◽  
E Coli ◽  
Resistance Determinants ◽  
16S Rna ◽  
Carbapenemase Gene

ABSTRACTThe resistome of the multidrug-resistantEscherichia colistrain 271 carrying the plasmid-mediatedblaNDM-1carbapenemase gene was analyzed by high-throughput genome sequencing. The p271A plasmid carrying theblaNDM-1gene was 35.9 kb in size and possessed an IncN-type backbone that harbored a novel replicase gene. Acquisition of theblaNDM-1gene on plasmid p271A had been likely the result of a cointegration event involving the transposase of Tn5403. The expression ofblaNDM-1was associated with the insertion sequence ISAba125likely originating fromAcinetobacter baumannii. E. coli271 accumulated multiple resistance determinants, including five β-lactamase genes (comprising the extended-spectrum β-lactamase CTX-M-15), two 16S RNA methylase ArmA- and RmtB-encoding genes, and theqepAgene encoding an efflux pump involved in resistance to fluoroquinolones. These resistance genes were located on three additional plasmids, of 160 kb (IncA/C), 130 kb (IncF), and 110 kb (IncI1). In addition, several chromosomally encoded resistance determinants were identified, such as topoisomerase mutations, porin modifications and truncations, and the intrinsicampCgene ofE. colithat was weakly expressed. The multidrug resistance pattern observed forE. coli271 was therefore the result of combined chromosome- and plasmid-encoded mechanisms.

scholarly journals Houseflies (Musca domestica) as Vectors for Extended-Spectrum β-Lactamase-Producing Escherichia coli on Spanish Broiler Farms

2015 ◽  
Vol 81 (11) ◽  
pp. 3604-3611 ◽  
Author(s):  
Marc Solà-Ginés ◽  
Juan José González-López ◽  
Karla Cameron-Veas ◽  
Nuria Piedra-Carrasco ◽  
Marta Cerdà-Cuéllar ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Ecological Niches ◽  
Potential Contribution ◽  
Content Type ◽  
Extended Spectrum Beta Lactamase ◽  
E Coli ◽  
Extended Spectrum

ABSTRACTFlies may act as potential vectors for the spread of resistant bacteria to different environments. This study was intended to evaluate the presence ofEscherichia colistrains resistant to cephalosporins in flies captured in the areas surrounding five broiler farms. Phenotypic and molecular characterization of the resistant population was performed by different methods: MIC determination, pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and phylotyping. The presence of extended-spectrum beta-lactamase (ESBL) genes, their plasmid location, and the mobile genetic elements involved in their mobilization were studied. Additionally, the presence of 35 genes associated with virulence was evaluated. Out of 682 flies captured, 42 yielded ESBL-producingE. coli. Of these isolates, 23 containedblaCTX-M-1, 18 containedblaCTX-M-14, and 1 containedblaCTX-M-9. ESBL genes were associated mainly with the presence of the IncI1 and IncFIB replicons. Additionally, all the strains were multiresistant, and five of them also harboredqnrS. Identical PFGE profiles were found forE. coliisolates obtained from flies at different sampling times, indicating a persistence of the same clones in the farm environment over months. According to their virulence genes, 81% of the isolates were considered avian-pathogenicE. coli(APEC) and 29% were considered extraintestinal pathogenicE. coli(ExPEC). The entrance of flies into broiler houses constitutes a considerable risk for colonization of broilers with multidrug-resistantE. coli. ESBLs in flies reflect the contamination status of the farm environment. Additionally, this study demonstrates the potential contribution of flies to the dissemination of virulence and resistance genes into different ecological niches.

scholarly journals Complete Genome Sequencing of Acinetobacter baumannii Strain K50 Discloses the Large Conjugative Plasmid pK50a Encoding Carbapenemase OXA-23 and Extended-Spectrum β-Lactamase GES-11

2018 ◽  
Vol 62 (5) ◽  
Author(s):  
Daniel Wibberg ◽  
Ileana P. Salto ◽  
Felix G. Eikmeyer ◽  
Irena Maus ◽  
Anika Winkler ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Genome Sequencing ◽  
Antibiotic Resistance Gene ◽  
Insertion Site ◽  
Multidrug Resistant ◽  
Conjugative Plasmid ◽  
Class 1 Integron ◽  
Content Type ◽  
Carbapenemase Gene ◽  
Class 1

ABSTRACT Multidrug-resistant (MDR) Acinetobacter baumannii strains appeared as serious emerging nosocomial pathogens in clinical environments and especially in intensive care units (ICUs). A. baumannii strain K50, recovered from a hospitalized patient in Kuwait, exhibited resistance to carbapenems and additionally to ciprofloxacin, chloramphenicol, sulfonamides, amikacin, and gentamicin. Genome sequencing revealed that the strain possesses two plasmids, pK50a (79.6 kb) and pK50b (9.5 kb), and a 3.75-Mb chromosome. A. baumannii K50 exhibits an average nucleotide identity (ANI) of 99.98% to the previously reported Iraqi clinical isolate AA-014, even though the latter strain lacked plasmid pK50a. Strain K50 belongs to sequence type 158 (ST158) (Pasteur scheme) and ST499 (Oxford scheme). Plasmid pK50a is a member of the Aci6 (replication group 6 [RG6]) group of Acinetobacter plasmids and carries a conjugative transfer module and two antibiotic resistance gene regions. The transposon Tn 2008 carries the carbapenemase gene bla OXA-23 , whereas a class 1 integron harbors the resistance genes bla GES-11 , aacA4 , dfrA7 , qacE Δ 1 , and sul1 , conferring resistance to all β-lactams and reduced susceptibility to carbapenems and resistance to aminoglycosides, trimethoprim, quaternary ammonium compounds, and sulfamethoxazole, respectively. The class 1 integron is flanked by MITEs (miniature inverted-repeat transposable elements) delimiting the element at its insertion site.

scholarly journals Fluorescence High-Throughput Screening for Inhibitors of TonB Action

2017 ◽  
Vol 199 (10) ◽  
Author(s):  
Brittany L. Nairn ◽  
Olivia S. Eliasson ◽  
Dallas R. Hyder ◽  
Noah J. Long ◽  
Aritri Majumdar ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Acinetobacter Baumannii ◽  
High Throughput ◽  
High Throughput Screening ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Content Type ◽  
E Coli ◽  
Compound Libraries

ABSTRACT Gram-negative bacteria acquire ferric siderophores through TonB-dependent outer membrane transporters (TBDT). By fluorescence spectroscopic hgh-throughput screening (FLHTS), we identified inhibitors of TonB-dependent ferric enterobactin (FeEnt) uptake through Escherichia coli FepA (EcoFepA). Among 165 inhibitors found in a primary screen of 17,441 compounds, we evaluated 20 in secondary tests: TonB-dependent ferric siderophore uptake and colicin killing and proton motive force-dependent lactose transport. Six of 20 primary hits inhibited TonB-dependent activity in all tests. Comparison of their effects on [59Fe]Ent and [14C]lactose accumulation suggested several as proton ionophores, but two chemicals, ebselen and ST0082990, are likely not proton ionophores and may inhibit TonB-ExbBD. The facility of FLHTS against E. coli led us to adapt it to Acinetobacter baumannii. We identified its FepA ortholog (AbaFepA), deleted and cloned its structural gene, genetically engineered 8 Cys substitutions in its surface loops, labeled them with fluorescein, and made fluorescence spectroscopic observations of FeEnt uptake in A. baumannii. Several Cys substitutions in AbaFepA (S279C, T562C, and S665C) were readily fluoresceinated and then suitable as sensors of FeEnt transport. As in E. coli, the test monitored TonB-dependent FeEnt uptake by AbaFepA. In microtiter format with A. baumannii, FLHTS produced Z′ factors 0.6 to 0.8. These data validated the FLHTS strategy against even distantly related Gram-negative bacterial pathogens. Overall, it discovered agents that block TonB-dependent transport and showed the potential to find compounds that act against Gram-negative CRE (carbapenem-resistant Enterobacteriaceae)/ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens. Our results suggest that hundreds of such chemicals may exist in larger compound libraries. IMPORTANCE Antibiotic resistance in Gram-negative bacteria has spurred efforts to find novel compounds against new targets. The CRE/ESKAPE pathogens are resistant bacteria that include Acinetobacter baumannii, a common cause of ventilator-associated pneumonia and sepsis. We performed fluorescence high-throughput screening (FLHTS) against Escherichia coli to find inhibitors of TonB-dependent iron transport, tested them against A. baumannii, and then adapted the FLHTS technology to allow direct screening against A. baumannii. This methodology is expandable to other drug-resistant Gram-negative pathogens. Compounds that block TonB action may interfere with iron acquisition from eukaryotic hosts and thereby constitute bacteriostatic antibiotics that prevent microbial colonization of human and animals. The FLHTS method may identify both species-specific and broad-spectrum agents against Gram-negative bacteria.

scholarly journals Clinical Use of Colistin Induces Cross-Resistance to Host Antimicrobials in Acinetobacter baumannii

mBio ◽  
2013 ◽  
Vol 4 (3) ◽  
Author(s):  
Brooke A. Napier ◽  
Eileen M. Burd ◽  
Sarah W. Satola ◽  
Stephanie M. Cagle ◽  
Susan M. Ray ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Multidrug Resistant ◽  
Innate Immune ◽  
Cross Resistance ◽  
Negative Consequences ◽  
Content Type ◽  
Bacterial Membranes ◽  
Before And After ◽  
New Antibiotics ◽  
Resistant Strains

ABSTRACTThe alarming rise in antibiotic resistance has led to an increase in patient mortality and health care costs. This problem is compounded by the absence of new antibiotics close to regulatory approval.Acinetobacter baumanniiis a human pathogen that causes infections primarily in patients in intensive care units (ICUs) and is highly antibiotic resistant. Colistin is one of the last-line antibiotics for treatingA. baumanniiinfections; however, colistin-resistant strains are becoming increasingly common. This cationic antibiotic attacks negatively charged bacterial membranes in a manner similar to that seen with cationic antimicrobials of the innate immune system. We therefore set out to determine if the increasing use of colistin, and emergence of colistin-resistant strains, is concomitant with the generation of cross-resistance to host cationic antimicrobials. We found that there is indeed a positive correlation between resistance to colistin and resistance to the host antimicrobials LL-37 and lysozyme among clinical isolates. Importantly, isolates obtained before and after treatment of individual patients demonstrated that colistin use correlated with increased resistance to cationic host antimicrobials. These data reveal the overlooked risk of inducing cross-resistance to host antimicrobials when treating patients with colistin as a last-line antibiotic.IMPORTANCEIncreased use of the cationic antibiotic colistin to treat multidrug-resistantAcinetobacter baumanniihas led to the development of colistin-resistant strains. Here we report that treatment of patients with colistin can induce not only increased resistance to colistin but also resistance to host cationic antimicrobials. This worrisome finding likely represents an example of a broader trend observed in other bacteria against which colistin is used therapeutically such asPseudomonas aeruginosaandKlebsiella pneumoniae. Furthermore, these data suggest that the possible future use of an array of cationic antimicrobial peptides in development as therapeutics may have unintended negative consequences, eventually leading to the generation of hypervirulent strains that are resistant to innate host defenses. The potential for the induction of cross-resistance to innate immune antimicrobials should be considered during the development of new therapeutics.

scholarly journals Tamoxifen repurposing to combat infections by multidrug-resistant Gram-negative bacilli

2020 ◽  
Author(s):  
Andrea Miró-Canturri ◽  
Rafael Ayerbe-Algaba ◽  
Raquel del Toro ◽  
Jerónimo Pachón ◽  
Younes Smani
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Immune System ◽  
Acinetobacter Baumannii ◽  
Therapeutic Efficacy ◽  
Multidrug Resistant ◽  
Tamoxifen Treatment ◽  
Resistant Bacteria ◽  
Gram Negative ◽  
E Coli

AbstractThe development of new strategic therapies for multidrug-resistant bacteria, like the use of non-antimicrobial approaches and/or drugs repurposing to be used as monotherapies or in combination with clinically relevant antibiotics, has become an urgent need. A therapeutic alternative for infections by multidrug-resistant Gram-negative bacilli (MDR-GNB) is immune system modulation to improve the infection clearance. We showed that immunocompetent mice infected by Acinetobacter baumannii, Pseudomonas aeruginosa or Escherichia coli in peritoneal sepsis models and treated with tamoxifen at 80 mg/kg/d for three days reduced the release of MCP-1 and its signalling pathway IL-18 and phosphorylated ERK1/2. This reduction of MCP-1 induced the reduction of migration of inflammatory monocytes and neutrophils from bone marrow to blood. Indeed, the treatment with tamoxifen in murine peritoneal sepsis models reduced the bacterial load in tissues and blood; and increased the mice survival from 0% to 60-100%. Tamoxifen treatment of neutropenic mice infected by these pathogens increased mice survival up to 20-60%. Furthermore, susceptibility and time-kill assays showed that the metabolites of tamoxifen, N-desmethyltamoxifen, hydroxytamoxifen and endoxifen, the three together exhibited MIC90 values of 16 mg/L and were bactericidal against clinical isolates of A. baumannii and E. coli. This antimicrobial activity of tamoxifen metabolites parallels’ an increased membrane permeability of A. baumannii and E. coli without affecting their outer membrane proteins profiles. Together, these data showed that tamoxifen present a therapeutic efficacy against MDR A. baumannii, P. aeruginosa and E. coli in experimental models of infections and can be repurposed as new treatment for GNB infections.ImportanceAntimicrobial resistance in Gram-negative bacilli (GNB) is a global health treat. Drug repurposing, a novel approach involving the search of new indications for FDA approved drugs is gaining interest. Among them, we found the anti-cancer drug tamoxifen, which presents very promising therapeutic efficacy. The current study showed that tamoxifen presents activity in animal models of infection with MDR Acinetobacter baumannii, Pseudomonas aeruginosa and Escherichia coli by modulating the traffic of innate immune system cells and the antibacterial activity presented by its three major metabolites produced in vivo against these GNB. Our results offer a new candidate to be repurposed to treat severe infections caused by these pathogens.

Synergistic Effect of Tazobactam on Amikacin MIC in Acinetobacter baumannii Isolated from Burn Patients in Tehran, Iran

2020 ◽  
Vol 21 (10) ◽  
pp. 997-1004
Author(s):  
Leila Azimi ◽  
Sahel V. Tahbaz ◽  
Reza Alaghehbandan ◽  
Farank Alinejad ◽  
Abdolaziz R. Lari
Keyword(s):  
Acinetobacter Baumannii ◽  
Inhibitory Concentration ◽  
Efflux Pump ◽  
Multidrug Resistant ◽  
Inhibitory Effect ◽  
Resistant Bacteria ◽  
High Morbidity ◽  
Burn Patients ◽  
Global Public Health ◽  
Before And After

Background: Burn is still an important global public health challenge. Wound colonization of antibiotic resistant bacteria such as Acinetobacter baumannii can lead to high morbidity and mortality in burn patients. The aim of this study was to evaluate the inhibitory effect of tazobactam on efflux pump, which can cause aminoglycoside resistant in A. baumannii isolated from burn patients. Methods: In this study, 47 aminoglycoside resistant A. baumannii spp. were obtained from burn patients, admitted to the Shahid Motahari Burns Hospital in Tehran, Iran, during June-August 2018. The inhibitory effect of tazobactam against adeB such as efflux pump was evaluated by Minimum Inhibitory Concentration (MIC) determination of amikacin alone and in combination with tazobactam. Fractional Inhibitory Concentration index (FIC) was used to determine the efficacy of tazobactam/ amikacin combination. Further, semi-quantitative Real- Time PCR was performed to quantify the expression rates of the adeB gene before and after addition of tazobactam/amikacin. Results: The MIC values were significantly reduced when a combined amikacin and tazobactam was utilized. The most common interaction observed was synergistic (78.2%), followed by additive effects (21.8%), as per FIC results. The adeB mRNA expression levels were found to be downregulated in 60.7% of isolates treated with tazobactam. Conclusions: Tazobactam can have impact on resistance to aminoglycoside by inhibiting efflux pump. Thus, the combination of tazobactam with amikacin can be used as an alternative treatment approach in multidrug resistant A. baumannii 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

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 In vitro activity of antimicrobial peptide CDP-B11 alone and in combination with colistin against colistin-resistant and multidrug-resistant Escherichia coli

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kaitlin S. Witherell ◽  
Jason Price ◽  
Ashok D. Bandaranayake ◽  
James Olson ◽  
Douglas R. Call
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Peptide ◽  
Membrane Integrity ◽  
Antibiotic Resistance Genes ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Multidrug Resistant Bacteria ◽  
E Coli ◽  
Minimal Media

AbstractMultidrug-resistant bacteria are a growing global concern, and with increasingly prevalent resistance to last line antibiotics such as colistin, it is imperative that alternative treatment options are identified. Herein we investigated the mechanism of action of a novel antimicrobial peptide (CDP-B11) and its effectiveness against multidrug-resistant bacteria including Escherichia coli #0346, which harbors multiple antibiotic-resistance genes, including mobilized colistin resistance gene (mcr-1). Bacterial membrane potential and membrane integrity assays, measured by flow cytometry, were used to test membrane disruption. Bacterial growth inhibition assays and time to kill assays measured the effectiveness of CDP-B11 alone and in combination with colistin against E. coli #0346 and other bacteria. Hemolysis assays were used to quantify the hemolytic effects of CDP-B11 alone and in combination with colistin. Findings show CDP-B11 disrupts the outer membrane of E. coli #0346. CDP-B11 with colistin inhibits the growth of E. coli #0346 at ≥ 10× lower colistin concentrations compared to colistin alone in Mueller–Hinton media and M9 media. Growth is significantly inhibited in other clinically relevant strains, such as Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae. In rich media and minimal media, the drug combination kills bacteria at a lower colistin concentration (1.25 μg/mL) compared to colistin alone (2.5 μg/mL). In minimal media, the combination is bactericidal with killing accelerated by up to 2 h compared to colistin alone. Importantly, no significant red blood hemolysis is evident for CDP-B11 alone or in combination with colistin. The characteristics of CDP-B11 presented here indicate that it can be used as a potential monotherapy or as combination therapy with colistin for the treatment of multidrug-resistant infections, including colistin-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.

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