TY  - JOUR
A1  - Betts, Jonathan
A1  - Nagel, Christopher
A1  - Schatzschneider, Ulrich
A1  - Poole, Robert
A1  - La Ragione, Robert M.
T1  - Antimicrobial activity of carbon monoxide-releasing molecule [Mn(CO)\(_3\)(tpa-\(\kappa^{3}N\))]Br versus multidrug-resistant isolates of Avian Pathogenic \(Escherichia\) \(coli\) and its synergy with colistin
JF  - PLoS ONE
N2  - Antimicrobial resistance is a growing global concern in human and veterinary medicine, with an ever-increasing void in the arsenal of clinicians. Novel classes of compounds including carbon monoxoide-releasing molecules (CORMs), for example the light-activated metal complex [Mn(CO)\(_3\)(tpa-\(\kappa^{3}N\))]Br, could be used as alternatives/to supplement traditional antibacterials. Avian pathogenic \(Escherichia\) \(coli\) (APEC) represent a large reservoir of antibiotic resistance and can cause serious clinical disease in poultry, with potential as zoonotic pathogens, due to shared serotypes and virulence factors with human pathogenic \(E.\) \(coli\). The \(in\) \(vitro\) activity of [Mn(CO)\(_3\)(tpa-\(\kappa^{3}N\))]Br against multidrug-resistant APECs was assessed via broth microtitre dilution assays and synergy testing with colistin performed using checkerboard and time-kill assays. \(In\) \(vivo\) antibacterial activity of [Mn(CO)\(_3\)(tpa-\(\kappa^{3}N\))]Br alone and in combination with colistin was determined using the \(Galleria\) \(mellonella\) wax moth larvae model. Animals were monitored for life/death, melanisation and bacterial numbers enumerated from larval haemolymph. \(In\) \(vitro\) testing produced relatively high [Mn(CO)\(_3\)(tpa-\(\kappa^{3}N\))]Br minimum inhibitory concentrations (MICs) of 1024 mg/L. However, its activity was significantly increased with the addition of colistin, bringing MICs down to \(\geq\)32 mg/L. This synergy was confirmed in time-kill assays. \(In\) \(vivo\) assays showed that the combination of [Mn(CO)\(_3\)(tpa-\(\kappa^{3}N\))]Br with colistin produced superior bacterial killing and significantly increased larval survival. In both \(in\) \(vitro\) and \(in\) \(vivo\) assays light activation was not required for antibacterial activity. This data supports further evaluation of [Mn(CO)\(_3\)(tpa-\(\kappa^{3}N\))]Br as a potential agent for treatment of systemic infections in humans and animals, when used with permeabilising agents such as colistin.
KW  - Chemistry
KW  - Larvae
KW  - Antibacterials
KW  - Antibiotics
KW  - Birds
KW  - Bacterial pathogens
KW  - Manganese
KW  - Antibiotic resistance
KW  - Antibacterial therapy
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173687
VL  - 12
IS  - 10
ER  - 
TY  - JOUR
A1  - Westermann, Alexander J.
A1  - Barquist, Lars
A1  - Vogel, Jörg
T1  - Resolving host-pathogen interactions by dual RNA-seq
JF  - PLoS Pathogens
N2  - The transcriptome is a powerful proxy for the physiological state of a cell, healthy or diseased. As a result, transcriptome analysis has become a key tool in understanding the molecular changes that accompany bacterial infections of eukaryotic cells. Until recently, such transcriptomic studies have been technically limited to analyzing mRNA expression changes in either the bacterial pathogen or the infected eukaryotic host cell. However, the increasing sensitivity of high-throughput RNA sequencing now enables “dual RNA-seq” studies, simultaneously capturing all classes of coding and noncoding transcripts in both the pathogen and the host. In the five years since the concept of dual RNA-seq was introduced, the technique has been applied to a range of infection models. This has not only led to a better understanding of the physiological changes in pathogen and host during the course of an infection but has also revealed hidden molecular phenotypes of virulence-associated small noncoding RNAs that were not visible in standard infection assays. Here, we use the knowledge gained from these recent studies to suggest experimental and computational guidelines for the design of future dual RNA-seq studies. We conclude this review by discussing prospective applications of the technique.
KW  - Medicine
KW  - RNA sequencing
KW  - Salmonellosis
KW  - Transcriptome analysis
KW  - Gene expression
KW  - Bacterial pathogens
KW  - Salmonella
KW  - Host cells
KW  - Lysis (medicine)
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171921
VL  - 13
IS  - 2
ER  -