SciCombinator

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Journal: Antimicrobial agents and chemotherapy

830

The recent discovery of a plasmid-borne colistin resistance gene, mcr-1, heralds the emergence of truly pan-drug resistant bacteria (1).….

Concepts: DNA, Gene, Bacteria, Genome, Antibiotic resistance, Escherichia coli, Plasmid, Proteobacteria

172

Multidrug resistance (MDR) plasmids frequently encode antibiotic resistance genes conferring qualitatively different mechanisms of resistance. We show that the antibiotic concentrations selecting for the RK2 plasmid in Escherichia coli depend upon the sociality of the drug resistance: Selection for a selfish drug resistance (efflux-pump) occurred at very low drug concentrations, just 1.3% of the sensitive’s MIC, whereas selection for a cooperative drug resistance (modifying-enzyme) occurred at drug concentrations exceeding the MIC of the plasmid-free strain.

Concepts: Gene, Natural selection, Bacteria, Genome, Antibiotic resistance, Escherichia coli, Plasmid, Bacterial conjugation

169

Pathogenic Leptospira spp., the causative agents of leptospirosis, are slow-growing Gram-negative spirochetes. Isolation of Leptospira from clinical samples and testing of antimicrobial susceptibility are difficult and time-consuming. Here, we describe the development of a new solid medium that facilitates more-rapid growth of Leptospira spp. and the use of this medium to evaluate the Etest’s performance in determining antimicrobial MICs to drugs in common use for leptospirosis. The medium was developed by evaluating the effects of numerous factors on the growth rate of Leptospira interrogans strain NR-20157. These included the type of base agar, the concentration of rabbit serum (RS), and the concentration and duration of CO(2) incubation during the initial period of culture. The highest growth rate of NR-20157 was achieved using a Noble agar base supplemented with 10% RS (named LVW agar), with an initial incubation at 30°C in 5% CO(2) for 2 days prior to continuous culture in air at 30°C. These conditions were used to develop the Etest for three species, L. interrogans (NR-20161), L. kirschnerii (NR-20327), and L. borgpetersenii (NR-20151). The MICs were read on day 7 for all samples. The Etest was then performed on 109 isolates of pathogenic Leptospira spp. The MIC(90) values for penicillin G, doxycycline, cefotaxime, ceftriaxone, and chloramphenicol were 0.64 units/ml and 0.19, 0.047, 0.5, and 2 μg/ml, respectively. The use of LVW agar, which enables rapid growth, isolation of single colonies, and simple antimicrobial susceptibility testing for Leptospira spp., provides an opportunity for new areas of fundamental and applied research.

Concepts: Microbiology, Penicillin, Spirochaetes, Spirochaete, Leptospira, Leptospirosis, The Medium, Causative

164

For its remarkable ability to acquire antibiotic resistance and to survive in nosocomial environments, Acinetobacter baumannii has become a significant nosocomial infectious agent worldwide. Tigecycline is one of the few therapeutic options to treat infections caused by A. baumannii isolates. However, tigecycline resistance has been increasingly reported. Our aim was to assess the prevalence and characteristics of efflux-based tigecycline resistance in clinical isolates of A. baumannii collected from a hospital in China. A total of 74 A. baumannii isolates including 64 tigecycline non-susceptible A. baumannii (TNAB) and 10 tigecycline susceptible A. baumannii (TSAB) isolates were analyzed. The majority of them were detected to be positive for adeABC, adeRS, adeIJK and abeM, while the adeE gene was found in only one TSAB isolate. Compared with TSAB isolates, the mean expression level of adeB, adeJ, adeG and abeM in TNAB isolates were observed to increase by 29-, 3-, 0.7- and 1-fold, respectively. The efflux pump inhibitors (EPIs) PAβN and carbonyl cyanide 3-chlorophenylhydrazone (CCCP) could partially reverse the resistance pattern of tigecycline. Moreover, tetX1 gene was detected in 12 (18.8%) TNAB isolates. To our knowledge, this is the first report that tetX1 gene was detected in the A. baumannii isolates. ST208 and ST191 which both clustered into clonal complex 92 (CC92) were the predominant sequence types (STs). This study showed that active efflux pump AdeABC appeared to play important roles in the tigecycline resistance of A. baumannii. The dissemination of TNAB isolates in our hospital is mainly attributable to the spread of CC92.

Concepts: Nosocomial infection, Antibiotic resistance, Antibiotic, Pseudomonadales, Acinetobacter baumannii, Acinetobacter, Tigecycline, Efflux

132

We present case histories of four patients treated with artemether-lumefantrine for falciparum malaria in UK hospitals in 2015-16. Each subsequently presented with recurrent symptoms and Plasmodium falciparum parasitaemia within 6 weeks of treatment with no intervening travel to malarious countries. Parasite isolates, all of African origin, harboured variants at some candidate resistance loci. No evidence of pfk13-mediated artemisinin resistance was found. Vigilance for signs of unsatisfactory antimalarial efficacy among imported cases of malaria is recommended.

Concepts: Malaria, Plasmodium falciparum, Plasmodium, Plasmodium vivax, Anopheles, Quinine, Apicomplexa, Artemisinin

60

42

Among 390 Escherichia coli and Klebsiella pneumoniae clinical isolates collected during 2014-2015 displaying colistin MIC values ≥4 μg/ml, 19 (4.9%) carried mcr-1 These isolates were all E. coli collected in ten countries, including the United States. Most isolates were susceptible to cephalosporins and were all susceptible to carbapenems, amikacin, tigecyline and ceftazidime-avibactam among other agents. Data from this global surveillance program expand the knowledge on the occurrence of mcr-1-carrying isolates.

Concepts: United States, Escherichia coli, Enterobacteriaceae, Escherichia, Proteobacteria, Beta-lactamase, Enterobacteria, Cephalosporin

40

Previous studies of antibiotic resistance dissemination by travel have, by targeting only a select number of cultivable bacterial species, omitted most of the human microbiome. Here, we used explorative shotgun metagenomic sequencing to address the abundance of >300 antibiotic resistance genes in fecal specimens from 35 Swedish students taken before and after exchange programs on the Indian peninsula or in central Africa. All specimens were additionally cultured for extended-spectrum beta-lactamase (ESBL) producing enterobacteria and the isolates obtained genome sequenced. The overall taxonomic diversity and composition of the gut microbiome remained stable comparing before and after travel, but with increasing abundance of Proteobacteria in 25/35 students. The relative abundance of antibiotic resistance genes increased, most prominently for genes encoding resistance to sulfonamide (2.6-fold increase), trimethoprim (7.7-fold) and beta-lactams (2.6-fold). Importantly, the increase observed occurred without any antibiotic intake. Of 18 students visiting the Indian peninsula, 12 acquired ESBL-producing Escherichia coli, while none returning from Africa was positive. Despite deep sequencing efforts, sensitivity of metagenomics was not sufficient to detect acquisition of the low-abundant genes responsible for the observed ESBL phenotype. In conclusion, metagenomic sequencing of the intestinal microbiome of Swedish students returning from exchange programs in Central Africa or the Indian peninsula showed increased abundance of genes encoding resistance to widely used antibiotics.

Concepts: Gene, Bacteria, Gut flora, Evolution, Africa, Antibiotic resistance, Escherichia coli, Beta-lactamase

30

SCY-078 is an orally bioavailable ß-1,3-glucan synthesis inhibitor (GSI) and the first-in-class of structurally novel triterpine antifungals in clinical development for treating candidemia and invasive candidiasis. In vitro susceptibility by broth micro-dilution, antifungal carry-over, and time-kill dynamics were determined for 3 reference (ATCC) strains (C. albicans 90028, C. parapsilosis 90018, and C. tropicalis 750), a Quality Control (QC) strain (C krusei 6258), and 4 other strains (C. albicans MYA-2732, 64124, 76485 and C.glabrata 90030). Caspofungin (CASP), fluconazole (FLC), and voriconazole (VRC) were comparators. For time-kill experiments, SCY-078 and CASP were evaluated at 0.25, 1, 2, 4, 8, and 16x MIC80, and FLU and VORI were evaluated at 4x MIC80 The time to reach 50%, 90%, and 99.9% growth from starting innoculum was determined. Net change in CFU/mL was used to determine EC50, EC90, and Emax SCY-078 MIC range was between 0.0625 - 1 μg/mL and generally similar to CASP. Antifungal carryover was not observed for SCY-078. SCY-078 was fungicidal against 7 isolates at ≥4x MIC (kill ≥3log10) and achieved a 1.7 log10 reduction in CFUs/mL against C. albicans 90028. CASP behaved similarly against each isolate and achieved a 1.5 log10 reduction in CFUs/mL against C. albicans 90028. Reductions of 50% in CFUs/mL were achieved rapidly (1-2.8 h); fungicidal endpoints were reached at 12.1 - 21.8 h at ≥4x MIC. EC90 was reached at ∼5x MIC at each time point to 24 h. EC50 and EC90 were generally similar (8-24 h). Time-kill behavior of CASP was similar to SCY-078. FLC and VRC were fungistatic. Overall, SCY-078 has primarily fungicidal activity against Candida spp. and behaved comparably to CASP.

Concepts: Candida albicans, Antifungals, Candidiasis, Candida, Fungemia, Antifungal drug, Fluconazole, Candida krusei

30

We have previously shown that SSYA10-001 blocks Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) replication by inhibiting SARS-CoV helicase (nsp13). Here, we show that SSYA10-001 also inhibits replication of two other coronaviruses, Mouse Hepatitis Virus (MHV) and Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV). A putative binding pocket for SSYA10-001 was identified and shown to be similar in SARS-CoV, MERS-CoV and MHV helicases. These studies show that it is possible to target multiple coronaviruses through broad-spectrum inhibitors.

Concepts: Severe acute respiratory syndrome, Enzyme inhibitor, Inhibitor, Xanthine oxidase inhibitor, SARS coronavirus, Coronavirus, Nidovirales, Mouse hepatitis virus