Chemical Communication of Antibiotic Resistance by Highly Resistant Bacteria.

The overall antibiotic resistance of a bacterial population results from the combination of a wide range of susceptibilities displayed by subsets of bacterial cells. Bacterial heteroresistance to antibiotics has been documented for several opportunistic Gram-negative bacteria, but the mechanism of heteroresistance is unclear. I use Burkholderia cenocepacia as a model opportunistic bacterium to investigate the implications of heterogeneity in the response to the antimicrobial peptide polymyxin B (PmB) and also other bactericidal antibiotics. Here, I report that B. cenocepacia is heteroresistant to PmB. Population analysis profiling identified B. cenocepacia subpopulations arising from a seemingly homogenous culture that are resistant to higher levels of PmB than the rest of the cells in the culture, and protect the more sensitive cells from killing, as well as sensitive bacteria from other species, such as Pseudomonas aeruginosa and Escherichia coli. Communication of resistance depended on upregulation of putrescine synthesis and YceI, a widely conserved low-molecular weight secreted protein. Deletion of genes for the synthesis of putrescine and YceI abrogate protection, while pharmacologic inhibition of putrescine synthesis reduced resistance to PmB. Polyamines and YceI were also required for heteroresistance of B. cenocepacia to various bactericidal antibiotics. I propose that putrescine and YceI resemble danger infochemicals whose increased production by a bacterial subpopulation, becoming more resistant to bactericidal antibiotics, communicates higher level of resistance to more sensitive members of the population of the same or different species. Putrescine protects from antibiotics through its ability to compete with PmB for surface binding and protection against antibiotic-induced oxidative stress. YceI proteins are conserved bacterial lipocalins or “bacteriocalins”. Bacteriocalins from different Gram-positive and Gram-negative bacteria are involved in the response to hydrophobic or amphiphilic antibiotics (PmB, rifampicin, norfloxacin and ceftazidime) but not hydrophilic ones (such as gentamicin). This effect is achieved by their preferential binding affinity to hydrophobic moieties. Together, my findings uncover a novel, non-genetic and cooperative mechanism of transient increase in resistance chemically communicated from more resistant members of heterogeneous populations to less resistant bacteria of the same or other species. This multifactorial mechanism of communication of antibiotic resistance offers novel targets for antimicrobial intervention

Antimicrobial Heteroresistance: an Emerging Field in Need of Clarity

“Heteroresistance” describes a phenomenon where subpopulations of seemingly isogenic bacteria exhibit a range of susceptibilities to a particular antibiotic. Unfortunately, a lack of standard methods to determine heteroresistance has led to inappropriate use of this term. Heteroresistance has been recognized since at least 1947 and occurs in Gram-positive and Gram-negative bacteria. Its clinical relevance may be considerable, since more resistant subpopulations may be selected during antimicrobial therapy. However, the use of nonstandard methods to define heteroresistance, which are costly and involve considerable labor and resources, precludes evaluating the clinical magnitude and severity of this phenomenon. We review the available literature on antibiotic heteroresistance and propose recommendations for definitions and determination criteria for heteroresistant bacteria. This will help in assessing the global clinical impact of heteroresistance and developing uniform guidelines for improved therapeutic outcomes

Draft genome sequence of an enterococcus faecalis strain (24FS) that was isolated from healthy infant feces and exhibits high antibacterial activity, multiple-antibiotic resistance, and multiple virulence factors

Enterococcus faecalis 24FS is a bacteriocin-producing, multiply antibiotic-resistant, and potentially virulent bacterium isolated from healthy infant feces. The draft 2.9-Mb genome sequence revealed 2,968 protein-encoding genes; 11 antibiotic resistance, 8 virulence, and 3 bacteriocin genes; and 2 plasmids, 4 prophages, 30 insertion sequence (IS) elements, 1 transposon, and 1 integron

Complete genome sequence of Lactobacillus plantarum 10CH, a potential probiotic lactic acid bacterium with potent antimicrobial aActivity

Lactobacillus plantarum 10CH is a bacteriocin-producing potential probiotic lactic acid bacterium (LAB) strain isolated from cheese. Its complete nucleotide sequence shows a single circular chromosome of 3.3 Mb, with a G+C content of 44.51%, a 25-gene plantaricin bacteriocin gene cluster, and the absence of recognized virulence factors. [Abstract copyright: Copyright © 2017 El Halfawy et al.

Antibiotic capture by bacterial lipocalins uncovers an extracellular mechanism of intrinsic antibiotic resistance

15 p.-6 fig.The potential for microbes to overcome antibiotics of different classes before they reach bacterial cells is largely unexplored. Here we show that a soluble bacterial lipocalin produced by Burkholderia cenocepacia upon exposure to sublethal antibiotic concentrations increases resistance to diverse antibiotics in vitro and in vivo. These phenotypes were recapitulated by heterologous expression in B. cenocepacia of lipocalin genes from Pseudomonas aeruginosa, Mycobacterium tuberculosis,and methicillin-resistant Staphylococcus aureus. Purified lipocalin bound different classes of bactericidal antibiotics and contributed to bacterial survival in vivo. Experimental and X-ray crystal structure-guided computational studies revealed that lipocalins counteract antibiotic action by capturing antibiotics in the extracellular space. We also demonstrated that fat-soluble vitamins prevent antibiotic capture by binding bacterial lipocalin with higher affinity than antibiotics. Therefore, bacterial lipocalins contribute to antimicrobial resistance by capturing diverse antibiotics in the extracellular space at the site of infection, which can be counteracted by known vitamins.This work was funded by grants from Cystic Fibrosis Canada, the European Commission,a Marie Curie Career Integration grant (projects 618095, NONANTIRES), and the Infection and Immunity Translational Research Group, Northern Ireland HSC to M.A.V.;the Spanish Ministry for Economy and Competitiveness (MINECO CTQ2011-22724 and CTQ2014-57141-R), European Commission Marie Curie grants GLYCOPHARM FP7-PITNGA-2012-317297 and TOLLerant H2020-MSC-ETN-642157 to S.M.S.; and Canadian Institutes of Health research grant MOP-49597 and a grant from Cystic Fibrosis Canada to M.E.P.M.Peer reviewe

A review on computer vision based defect detection and condition assessment of concrete and asphalt civil infrastructure

To ensure the safety and the serviceability of civil infrastructure it is essential to visually inspect and assess its physical and functional condition. This review paper presents the current state of practice of assessing the visual condition of vertical and horizontal civil infrastructure; in particular of reinforced concrete bridges, precast concrete tunnels, underground concrete pipes, and asphalt pavements. Since the rate of creation and deployment of computer vision methods for civil engineering applications has been exponentially increasing, the main part of the paper presents a comprehensive synthesis of the state of the art in computer vision based defect detection and condition assessment related to concrete and asphalt civil infrastructure. Finally, the current achievements and limitations of existing methods as well as open research challenges are outlined to assist both the civil engineering and the computer science research community in setting an agenda for future research

Efficacy and Safety of Tunneled Pleural Catheters in Adults with Malignant Pleural Effusions: A Systematic Review

BackgroundMalignant pleural effusions (MPE) are a frequent cause of dyspnea and discomfort at the end of cancer patients' lives. The tunneled indwelling pleural catheter (TIPC) was approved by the FDA in 1997 and has been investigated as a treatment for MPE.ObjectiveTo systematically review published data on the efficacy and safety of the TIPC for treatment of MPE.DesignWe searched the MEDLINE, EMBASE, and ISI Web of Science databases to identify studies published through October 2009 that reported outcomes in adult patients with MPE treated with a TIPC. Data were aggregated using summary statistics when outcomes were described in the same way among multiple primary studies.Main measuresSymptomatic improvement and complications associated with use of the TIPC.Key resultsNineteen studies with a total of 1,370 patients met criteria for inclusion in the review. Only one randomized study directly compared the TIPC with the current gold standard treatment, pleurodesis. All other studies were case series. Symptomatic improvement was reported in 628/657 patients (95.6%). Quality of life measurements were infrequently reported. Spontaneous pleurodesis occurred in 430/943 patients (45.6%). Serious complications were rare and included empyema in 33/1168 patients (2.8%), pneumothorax requiring a chest tube in 3/51 (5.9%), and unspecified pneumothorax in 17/439 (3.9%). Minor complications included cellulitis in 32/935 (3.4%), obstruction/clogging in 33/895 (3.7%) and unspecified malfunction of the catheter in 11/121 (9.1%). The use of the TIPC was without complication in 517/591 patients (87.5%).ConclusionsBased on low-quality evidence in the form of case series, the TIPC may improve symptoms for patients with MPE and does not appear to be associated with major complications. Prospective randomized studies comparing the TIPC to pleurodesis are needed before the TIPC can be definitively recommended as a first-line treatment of MPE

Phenotypic heterogeneity in fungi: importance and methodology

Phenotypic heterogeneity describes the variation that exists between individual cells, spores or other biological entities within genetically-uniform populations of fungi or other organisms. Studies over the last 10-15 years have successfully used laboratory- and modelling-based approaches to demonstrate the prevalence of phenotypic heterogeneity and characterise the molecular bases of the phenomenon (primarily centred around heterogeneous gene expression). In contrast to progress in these areas, the relevance of phenotypic heterogeneity for the competitive success of organisms in different natural scenarios, although widely speculated upon, has only recently begun to be investigated. This focus review addresses this latter question as tackled in recent studies with yeasts and filamentous fungi. We concentrate on the relevance to fungal activities such as survival against environmental stressors, pathogenesis, and spoilage. We also discuss methodologies for interrogating phenotypic heterogeneity in fungi. The emerging prevalence and apparent importance of fungal phenotypic heterogeneity provides a timely reminder that certain, potentially core aspects of fungal biology still remain widely under-explored