- Does Treatment Order Matter? Investigating the Ability of Bacteriophage to Augment Antibiotic Activity againstStaphylococcus aureusBiofilms. [Journal Article]
- FMFront Microbiol 2018; 9:127
- The inability to effectively treat biofilm-related infections is a major clinical challenge. This has been attributed to the heightened antibiotic tolerance conferred to bacterial cells embedded with...
The inability to effectively treat biofilm-related infections is a major clinical challenge. This has been attributed to the heightened antibiotic tolerance conferred to bacterial cells embedded within biofilms. Lytic bacteriophages (phages) have evolved to effectively infect and eradicate biofilm-associated cells. The current study was designed to investigate the ability of phage treatment to enhance the activity of antibiotics against biofilm-formingStaphylococcus aureus. The biofilm positiveS. aureusstrain ATCC 35556, the lyticS. aureusphage SATA-8505, and five antibiotics (cefazolin, vancomycin, dicloxacillin, tetracycline, and linezolid), used to treatS. aureusinfections, were tested in this study. The ability of the SATA-8505 phage to augment the effect of these antibiotics against biofilm-associatedS. aureuscells was assessed by exposing them to one of the five following treatment strategies: (i) antibiotics alone, (ii) phage alone, (iii) a combination of the two treatments simultaneously, (iv) staggered exposure to the phage followed by antibiotics, and (v) staggered exposure to antibiotics followed by exposure to phage. The effect of each treatment strategy on biofilm cells was assessed by enumerating viable bacterial cells. The results demonstrate that the treatment of biofilms with either SATA-8505, antibiotics, or both simultaneously resulted in minimal reduction of viable biofilm-associated cells. However, a significant reduction [up to 3 log colony forming unit (CFU)/mL] was observed when the phage treatment preceded antibiotics. This effect was most pronounced with vancomycin and cefazolin which exhibited synergistic interactions with SATA-8505, particularly at lower antibiotic concentrations. Thisin vitrostudy provides proof of principle for the ability of phages to augment the activity of antibiotics againstS. aureusbiofilms. Our results also demonstrate that therapeutic outcomes can be influenced by the sequence in which these therapeutic agents are administered, and the nature of their interactions. Further investigation into the interactions between lytic phages and antibiotics against various biofilm-forming organisms is important to direct future clinical translation of efficacious antibiotic-phage combination therapeutic strategies.
- Attenuation of neuro-inflammation improves survival and neurodegeneration in a mouse model of severe neonatal hyperbilirubinemia. [Journal Article]
- BBBrain Behav Immun 2018 Feb 16
- All pre-term newborns and a high proportion of term newborns develop neonatal jaundice. Neonatal jaundice is usually a benign condition and self-resolves within few days after birth. However, a combi...
All pre-term newborns and a high proportion of term newborns develop neonatal jaundice. Neonatal jaundice is usually a benign condition and self-resolves within few days after birth. However, a combination of unfavorable complications may lead to acute hyperbilirubinemia. Excessive hyperbilirubinemia may be toxic for the developing nervous system leading to severe neurological damage and death by kernicterus. Survivors show irreversible neurological deficits such as motor, sensitive and cognitive abnormalities. Current therapies rely on the use of phototherapy and, in unresponsive cases, exchange transfusion, which is performed only in specialized centers. During bilirubin-induced neurotoxicity different molecular pathways are activated, ranging from oxidative stress to endoplasmic reticulum (ER) stress response and inflammation, but the contribution of each pathway in the development of the disease still requires further investigation. Thus, to increase our understanding of the pathophysiology of bilirubin neurotoxicity, encephalopathy and kernicterus, we pharmacologically modulated neurodegeneration and neuroinflammation in a lethal mouse model of neonatal hyperbilirubinemia. Treatment of mutant mice with minocycline, a second-generation tetracycline with anti-inflammatory and neuroprotective properties, resulted in a dose-dependent rescue of lethality, due to reduction of neurodegeneration and neuroinflammation, without affecting plasma bilirubin levels. In particular, rescued mice showed normal motor-coordination capabilities and behavior, as determined by the accelerating rotarod and open field tests, respectively. From the molecular point of view, rescued mice showed a dose-dependent reduction in apoptosis of cerebellar neurons and improvement of dendritic arborization of Purkinje cells. Moreover, we observed a decrease of bilirubin-induced M1 microglia activation at the sites of damage with a reduction in oxidative and ER stress markers in these cells. Collectively, these data indicate that neurodegeneration and neuro-inflammation are key factors of bilirubin-induced neonatal lethality and neuro-behavioral abnormalities. We propose that the application of pharmacological treatments having anti-inflammatory and neuroprotective effects, to be used in combination with the current treatments, may significantly improve the management of acute neonatal hyperbilirubinemia, protecting from bilirubin-induced neurological damage and death.
- Occurrence and transformation of veterinary antibiotics and antibiotic resistance genes in dairy manure treated by advanced anaerobic digestion and conventional treatment methods. [Journal Article]
- EPEnviron Pollut 2018 Feb 15; 236:764-772
- Manure treatment technologies are rapidly developing to minimize eutrophication of surrounding environments and potentially decrease the introduction of antibiotics and antibiotic resistant genes (AR...
Manure treatment technologies are rapidly developing to minimize eutrophication of surrounding environments and potentially decrease the introduction of antibiotics and antibiotic resistant genes (ARGs) into the environment. While laboratory and pilot-scale manure treatment systems boast promising results, antibiotic and ARG removals in full-scale systems receiving continuous manure input have not been evaluated. The effect of treatment on ARGs is similarly lacking. This study examines the occurrence and transformation of sulfonamides, tetracyclines, tetracycline degradation products, and related ARGs throughout a full-scale advanced anaerobic digester (AAD) receiving continuous manure and antibiotic input. Manure samples were collected throughout the AAD system to evaluate baseline antibiotic and ARG input (raw manure), the effect of hygenization (post-pasteurized manure) and anaerobic digestion (post-digestion manure) on antibiotic and ARG levels. Antibiotics were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the ARGs tet(O), tet(W), sul1 and sul2 were analyzed by quantitative polymerase chain reaction (Q-PCR). Significant reductions in the concentrations of chlortetracycline, oxytetracycline, tetracycline and their degradation products were observed in manure liquids following treatment (p < 0.001), concomitant to significant increases in manure solids (p < 0.001). These results suggest sorption is the major removal route for tetracyclines during AAD. Significant decreases in the epimer-to-total residue ratios for chlortetracycline and tetracycline in manure solids further indicate degradation is desorption-limited. Moreover, sul1 and sul2 copies decreased significantly (p < 0.001) following AAD in the absence of sulfonamide antibiotics, while tetracyclines-resistant genes remained unchanged. A cross-sectional study of dairy farms utilizing natural aeration and liquid-solid separation treatments was additionally performed to compare levels of antibiotics and ARGs found in AAD with the levels in common manure management systems. The concentration of antibiotics in raw manure varied greatly between farms while minimal differences in ARGs were observed. However, significant (p < 0.01) differences in the levels of antibiotics and ARGs (except tet(W)) were observed in the effluents from the three different manure management systems.
- Effect of adding low-concentration of rhamnolipid on reactor performances and microbial community evolution in MBBRs for low C/N ratio and antibiotic wastewater treatment. [Journal Article]
- BTBioresour Technol 2018 Feb 08
- This study aims to explore the potential of low-concentration of rhamnolipid in efficient treatment of wastewater with poor biodegradability. Six lab-scale moving bed biofilm reactors (MBBRs) were ap...
This study aims to explore the potential of low-concentration of rhamnolipid in efficient treatment of wastewater with poor biodegradability. Six lab-scale moving bed biofilm reactors (MBBRs) were applied to investigate the effect of rhamnolipid concentration (0, 20, 50 mg/L) on pollutants removal, biomass accumulation, microbial morphology and community evolution in synthetic low C/N ratio (3:1) and antibiotic (50 μg/L tetracycline) wastewater. 20 mg/L rhamnolipid treated groups exhibited significant increase (p < 0.05) of chemical oxygen demand (COD) removal and volatile solid (VS) content in both synthetic wastewater. Hydrogenophaga and Aeromonas were dominant in all reactors in which Aeromonas was positively correlated with the removal of COD and ammonia nitrogen (NH4+-N). Besides, Methyloversatilis became dominant only in 20 mg/L rhamnolipid treated groups and was positively correlated with VS. This study provides a novel and feasible strategy for treating poorly biodegradable wastewater by biofilm process with moderate amount of rhamnolipid.
- Investigating antibiotics, antibiotic resistance genes, and microbial contaminants in groundwater in relation to the proximity of urban areas. [Journal Article]
- EPEnviron Pollut 2018 Feb 14; 236:734-744
- Groundwater is an essential public and drinking water supply and its protection is a goal for global policies. Here, we investigated the presence and prevalence of antibiotic residues, antibiotic res...
Groundwater is an essential public and drinking water supply and its protection is a goal for global policies. Here, we investigated the presence and prevalence of antibiotic residues, antibiotic resistance genes (ARGs), mobile genetic elements (MGEs), and microbial contamination in groundwater environments at various distances from urban areas. Antibiotic concentrations ranged from below detection limit to 917 ng/L, being trimethoprim, macrolide, and sulfonamide the most abundant antibiotic classes. A total of eleven ARGs (aminoglycoside, β-lactam, chloramphenicol, Macrolide-Lincosamide-Streptogramin B - MLSB, sulfonamide, and tetracycline), one antiseptic resistance gene, and two MGEs were detected by qPCR with relative abundances ranging from 6.61 × 10-7to 2.30 × 10-1copies/16S rRNA gene copies. ARGs and MGEs were widespread in the investigated groundwater environments, with increased abundances not only in urban, but also in remote areas. Distinct bacterial community profiles were observed, with a higher prevalence of Betaproteobacteria and Bacteroidetes in the less-impacted areas, and that of Firmicutes in the contaminated groundwater. The combined characteristics of increased species diversity, distinct phylogenetic composition, and the possible presence of fecal and/or pathogenic bacteria could indicate different types of contamination. Significant correlations between ARGs, MGEs and specific taxa within the groundwater bacterial community were identified, revealing the potential hosts of resistance types. Although no universal marker gene could be determined, a co-selection of int1, qacEΔ1 and sulI genes, a proxy group for anthropogenic pollution, with the tetC, tetO, tetW resistance genes was identified. As the tet group was observed to follow the pattern of environmental contamination for the groundwater samples investigated in this study, our results strongly support the proposal of this group of genes as an environmental tracer of human impact. Overall, the present study investigated several emerging contaminants in groundwater habitats that may be included in monitoring programs to enable further regulatory and protection measures.
- Seasonal dynamics of tetracycline resistance gene transport in the Sumas River agricultural watershed of British Columbia, Canada. [Journal Article]
- STSci Total Environ 2018 Feb 13; 628-629:490-498
- Environmental transport of contaminants that can influence the development of antibiotic resistance in bacteria is an important concern in the management of ecological and human health risks. Agricul...
Environmental transport of contaminants that can influence the development of antibiotic resistance in bacteria is an important concern in the management of ecological and human health risks. Agricultural regions are locales where practices linked to food crop and livestock production can introduce contaminants that could alter the selective pressures for the development of antibiotic resistance in microbiota. This is important in regions where the use of animal manure or municipal biosolids as waste and/or fertilizer could influence selection for antibiotic resistance in pathogenic bacterial species. To investigate the environmental transport of contaminants that could lead to the development of antibiotic resistance in bacteria, a watershed with one of the highest levels of intensity of agricultural activity in Canada was studied; the Sumas River located 60 km east of Vancouver, British Columbia. This two-year assessment monitored four selected tetracycline resistance genes (tet(O), tet(M), tet(Q), tet(W)) and water quality parameters (temperature, specific conductivity, turbidity, suspended solids, nitrate, phosphate and chloride) at eight locations across the watershed. The tetracycline resistance genes (Tcr) abundances in the Sumas River network ranged between 1.47 × 102and 3.49 × 104 copies/mL and ranged between 2.3 and 6.9 copies/mL in a control stream (located far from agricultural activities) for the duration of the study. Further, Tcrabundances that were detected in the wet season months ranged between 1.3 × 103and 2.29 × 104 copies/mL compared with dry season months (ranging between 0.6 and 31.2 copies/mL). Highest transport rates between 1.67 × 1011and 1.16 × 1012 copies/s were observed in November 2005 during periods of high rainfall. The study showed that elevated concentrations of antibiotic resistance genes in the order of 102-104 copies/mL can move through stream networks in an agricultural watershed but seasonal variations strongly influenced specific transport patterns of these genes.
- Antibiotic resistance along an urban river impacted by treated wastewaters. [Journal Article]
- STSci Total Environ 2018 Feb 13; 628-629:453-466
- Urban rivers are impacted ecosystems which may play an important role as reservoirs for antibiotic-resistant (AR) bacteria. The main objective of this study was to describe the prevalence of antibiot...
Urban rivers are impacted ecosystems which may play an important role as reservoirs for antibiotic-resistant (AR) bacteria. The main objective of this study was to describe the prevalence of antibiotic resistance along a sewage-polluted urban river. Seven sites along the Zenne River (Belgium) were selected to study the prevalence of AR Escherichia coli and freshwater bacteria over a 1-year period. Culture-dependent methods were used to estimate E. coli and heterotrophic bacteria resistant to amoxicillin, sulfamethoxazole, nalidixic acid and tetracycline. The concentrations of these four antibiotics have been quantified in the studied river. The antibiotic resistance genes (ARGs), sul1, sul2, tetW, tetO, blaTEM and qnrS were also quantified in both particle-attached (PAB) and free-living (FLB) bacteria. Our results showed an effect of treated wastewaters release on the spread of antibiotic resistance along the river. Although an increase in the abundance of both AR E. coli and resistant heterotrophic bacteria was observed from upstream to downstream sites, the differences were only significant for AR E. coli. A significant positive regression was also found between AR E. coli and resistant heterotrophic bacteria. The concentration of ARGs increased from upstream to downstream sites for both particle-attached (PAB) and free-living bacteria (FLB). Particularly, a significant increase in the abundance of four among six ARGs analyzed was observed after crossing urban area. Although concentrations of tetracycline significantly correlated with tetracycline resistance genes, the antibiotic levels were likely too low to explain this correlation. The analysis of ARGs in different fractions revealed a significantly higher abundance in PAB compared to FLB for tetO and sul2 genes. This study demonstrated that urban activities may increase the spread of antibiotic resistance even in an already impacted river.
- Primary antibiotic resistance and its relationship with cagA and vacA genes in Helicobacter pylori isolates from Algerian patients. [Journal Article]
- BJBraz J Microbiol 2018 Feb 13
- The epidemiology of Helicobacter pylori resistance to antibiotics is poorly documented in Africa and especially in Algeria. The aim of our study was to determine the antibiotic resistance rates, as w...
The epidemiology of Helicobacter pylori resistance to antibiotics is poorly documented in Africa and especially in Algeria. The aim of our study was to determine the antibiotic resistance rates, as well as its possible relationship with VacA and CagA virulence markers of isolates from Algerian patients. One hundred and fifty one H. pylori isolate were obtained between 2012 and 2015 from 200 patients with upper abdominal pain. Antimicrobial susceptibility testing was performed for amoxicillin, clarithromycin, metronidazole, ciprofloxacin, rifampicin and tetracycline. Molecular identification of H. pylori and the detection of vacA and cagA genes were performed using specific primers. We found that H. pylori was present in 83.5% of collected biopsies, 54.9% of the samples were cagA positive, 49.67% were vacA s1m1, 18.30% were vacA s1m2 and 25.49% were vacA s2m2. Isolates were characterized by no resistance to amoxicillin (0%), tetracycline (0%), rifampicin (0%), a high rate of resistance to metronidazole (61.1%) and a lower rate of resistance to clarithromycin (22.8%) and ciprofloxacin (16.8%). No statically significant relationship was found between vagA and cagA genotypes and antibiotic resistance results (p>0.5) except for the metronidazole, which had relation with the presence of cagA genotype (p=0.001).
- CC398 Staphylococcus aureus subpopulations in Belgian patients. [Journal Article]
- EJEur J Clin Microbiol Infect Dis 2018 Feb 15
- Studies based on genome-wide single nucleotide polymorphisms (SNPs) supported the existence of two subpopulations in clonal complex (CC) 398 Staphylococcus aureus: an ancestral human-adapted clade (H...
Studies based on genome-wide single nucleotide polymorphisms (SNPs) supported the existence of two subpopulations in clonal complex (CC) 398 Staphylococcus aureus: an ancestral human-adapted clade (HC) and an animal-associated clade (AC). In this study, we have investigated the occurrence of genetic markers that allow discrimination of these subpopulations among CC398 isolates collected during 2014 to 2016 from human patients in Belgium. A collection of isolates was investigated by means of spa-typing and 16S-mecA-nuc PCR. CC398 isolates were classified as belonging to the human or the animal clade by using a canonical SNPs PCR and further studied by antimicrobial susceptibility and the presence of toxins, immune evasion cluster (IEC), and resistance genes. A total of 124 (7.8%) human isolates belonged to CC398. They were grouped into HC (n = 58) or AC (n = 66). The genes erm(T), pvl, chp, and scn were predominantly found in HC-CC398, while AC-CC398 isolates carried more frequently than the mecA, erm(C), tet(K), tet(M), and tet(L) genes. Different combinations of gene profiles were observed according to the clade. CC398 isolates from Belgian patients belonged to different subpopulations including typical HC and AC-isolates. Few HC-strains with mecA and AC-isolates harboring IEC were found. CC398 isolates from Belgian patients belonged to different subpopulations including typical HC and AC-isolates, as well as new emerging subpopulations that underline the ability of this lineage to acquire resistance and virulence genes. Further research is needed to evaluate the emergence of these subpopulations in the clinical setting.
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- Whole genome sequencing of multidrug-resistantSalmonella entericaserovar Typhimurium isolated from humans and poultry in Burkina Faso. [Journal Article]
- TMTrop Med Health 2018; 46:4
- CONCLUSIONS: The poultry and human isolates were genetically similar showing a potential food safety risk for consumers. Our finding of multidrug-resistantS.Typhimurium ST313 in poultry feces calls for further studies to clarify the potential reservoirs of this emerging pathogen.