scholarly journals The efficacy of antimicrobial agents is decreased in a polymicrobial environment

2021 ◽  
Author(s):  
Thomas James O'Brien ◽  
Wendy Figueroa ◽  
Martin Welch

The airways of people with cystic fibrosis (CF) often harbour diverse polymicrobial communities. These airway infections can be impossible to resolve though antibiotic intervention, even though isolates of the individual species present are susceptible to the treatment when tested in vitro. This suggests that susceptibility to antimicrobial agents may be altered in the presence of other microbial species. In this work, we investigate how polymicrobial cultures of key CF-associated species respond to challenge with species-specific antimicrobial agents; colistin (targets Pseudomonas aeruginosa), fusidic acid (targets Staphylococcus aureus) and fluconazole (targets Candida albicans). We found that, compared with growth in axenic cultures, the target organism was protected (sometimes by several orders of magnitude) from the effect(s) of the antimicrobial agent when grown in a polymicrobial culture. This decreased antimicrobial efficacy in polymicrobial cultures was found to have both phenotypic and inherited components. Whole genome sequencing of the colistin-resistant P. aeruginosa isolates revealed single nucleotide polymorphisms and indels in genes encoding lipopolysaccharide (LPS) biosynthesis or pilus biogenesis. Colistin resistance associated with loss-of-function mutations in the LPS biosynthetic gene, wzy, could be complemented by expression of the wild-type wzy gene in trans. Our findings indicate that the polymicrobial nature of the CF airways is likely to have a significant impact on the clinical response to antimicrobial therapy.

2015 ◽  
Vol 24 (1) ◽  
pp. 34-40 ◽  
Author(s):  
B. P. Heyojoo ◽  
S. Nandy

This study aims to estimate above-ground phytomass and carbon of TROF ecosystem in part of Bijnor district in Uttar Pradesh state of India using IRS P6 LISS-IV satellite image by geo-spatial approach coupled with field sampling. Chacko’s formula was referred to compute number of samples in each TROF types and the sample plot size in each stratum was adopted from Vegetation Carbon Project (VCP) under National Carbon Project (NCP). With the help of field data consisting mainly the height and girth information, volume of each individual tree per plot was obtained using site and tree species-specific standard volumetric equations. The phytomass was calculated by multiplying volume with Biomass Expansion Factor (BEF) then with regional specific gravity of the individual species and summed up in each plot to get total phytomass per plot. The total phytomass per plot was reported to be maximum 544.00 t/ha for linear TROF followed by 121.89 t/ha for block TROF. The carbon from phytomass was obtained by multiplying the total phytomass by a conversion factor that represents the average carbon content in phytomass. Spectral modeling for phytomass with different bands and indices were established and the best fit curve (R2 = 0.552) with red band was applied to generate phytomass and carbon distribution map of the study area.Banko Janakari, Vol. 24, No. 1, pp. 34-40


Author(s):  
B.J. Wills ◽  
G.B. Douglas ◽  
J. Mckenzie ◽  
K.D. Trainor ◽  
A.G. Foote

Intermediate and pubescent wheatgrasses (Thinopyrum intermedium) are potentially useful as dryland forage grasses in New Zealand. The recent literature on their international and local use in pasture and cropping situations is reviewed. Under semi-arid conditions at Bendigo Station over a 13-year period, cv. Luna wheatgrass has spread several metres from the original drill lines and it provides very high ground cover. In terms of dryland soil resource conservation this contrasts with adjacent cocksfoot and, to a lesser extent, lucerne plots which have wide-spaced plants interspersed with litter and much bare ground. In a mixed drilling containing wheatgrass, hairy dorycnium, birdsfoot trefoil and sheep's burnet, the first two species now dominate. At Takapau, central Hawke's Bay, annual yields from intermediate and pubescent wheatgrasses produced over 80% of the yield of 10 New Zealand cultivars in spring, summer and autumn, and 65% in the winter. Of the wheatgrasses, cv. Topar intermediate wheatgrass and a pubescent wheatgrass (unnamed line) were the lowest yielding, whereas cv. Oahe and cv. Mandan produced the highest yields. Cv. Greenleaf pubescent wheatgrass had higher foliar nitrogen content than all other species, but in vitro organic matter digestibility was less than 700 g OM/kg DM. Although the wheatgrasses had satisfactory herbage yield and nutritional value, better alternative species are available for pastoral farming in central Hawke's Bay. On Belfield in the Hakataramea Valley, cv. Rush has been the most vigorous wheatgrass for establishment and it seems to handle cold winds and frost well. Hay made from a wheatgrass/ lucerne mix is considered better than that from the individual species as this can increase production by 40-50%, depending on soil and climatic conditions. Usually only one cut per year is taken from the mixed pasture. Crop maintenance includes the application of 200 kg/ha of sulphur super extra every 3-4 years and the pH is maintained at about 5.9-6.4 by liming. A significant advantage is that no stock health, pest or plant disease problems have been noted as yet with any of the wheatgrass varieties available in New Zealand. Keywords: dryland agriculture, New Zealand, Thinopyrum, wheatgrass


2007 ◽  
Vol 51 (11) ◽  
pp. 4071-4076 ◽  
Author(s):  
Yoshihisa Kohno ◽  
Hideaki Ohno ◽  
Yoshitsugu Miyazaki ◽  
Yasuhito Higashiyama ◽  
Katsunori Yanagihara ◽  
...  

ABSTRACT The recommended treatments for Mycobacterium avium complex (MAC) infectious disease are combination regimens of clarithromycin (CLR) or azithromycin with ethambutol and rifamycin. However, these chemotherapy regimens are sometimes unsuccessful. Recently developed antimicrobial agents, such as newer fluoroquinolones (FQs) containing C-8 methoxy quinolone (moxifloxacin [MXF] and gatifloxacin [GAT]), are expected to be novel antimycobacterial agents. Here, we evaluated the in vitro and in vivo antimycobacterial activities of three FQs (MXF, GAT, and levofloxacin) and CLR against clinically isolated MAC strains. Subsequently, the in vitro and in vivo synergic activities of FQ-CLR combinations against MAC strains were investigated. CLR and the individual FQs alone showed promising activity against MAC strains in vitro, and the bacterial counts in organs (lungs, liver, and spleen) of MAC-infected mice treated with single agents were significantly reduced compared to control mice. CLR showed the best anti-MAC effect in vivo. When the three FQs were individually combined with CLR in vitro, mild antagonism was observed for 53 to 57% of the tested isolates. Moreover, mice were infected with MAC strains showing mild antagonism for FQ-CLR combinations in vitro, and the anti-MAC effects of the FQ-CLR combinations were evaluated by counting the viable bacteria in their organs and by histopathological examination after 28 days of treatment. Several FQ-CLR combinations exhibited bacterial counts in organs significantly higher than those in mice treated with CLR alone. Our results indicate that the activity of CLR is occasionally attenuated by combination with an FQ both in vitro and in vivo and that this effect seems to be MAC strain dependent. Careful combination chemotherapy using these agents against MAC infectious disease may be required.


2001 ◽  
Vol 46 (No. 9–10) ◽  
pp. 237-240 ◽  
Author(s):  
A. Lauková ◽  
I. Štyriak ◽  
M. Mareková

Enterococci and staphylococci, isolates from faecal samples of 46 different animals such as deer, chamois, European bison, zebra, camel, antelope, gazelle, horse, and piglets were treated by nisin (concentration 1 mg/ml). Only two strains (SX38 and EA163), isolates from the faeces of deer were not inhibited by nisin under in vitro conditions. It means 97.4% of target isolates were inhibited by nisin and 2.6% were resistant. The majority of microorganisms were inhibited by nisin under MIC 1.56–100 µg/ml. Twenty-two percent out of 77 isolates were inhibited by MIC of nisin 3.12 µg.Enterococcus sp. E6B strain was found the most sensitive (inhibition by MIC 1.56 µg of nisin). Although only a few staphylococci were tested, most of them were inhibited by nisin. Even though the effect of nisin on the individual species was not evaluated, its effect on the group of bacteria is already important. In general, the properties of nisin indicate a broad spectrum of its utilization.


2008 ◽  
Vol 7 (3) ◽  
pp. 483-492 ◽  
Author(s):  
Yue Fu ◽  
Guanpingsheng Luo ◽  
Brad J. Spellberg ◽  
John E. Edwards ◽  
Ashraf S. Ibrahim

ABSTRACT We developed a conditional overexpression/suppression genetic strategy in Candida albicans to enable simultaneous testing of gain or loss of function in order to identify new virulence factors. The strategy involved insertion of a strong, tetracycline-regulated promoter in front of the gene of interest. To validate the strategy, a library of genes encoding glycosylphosphatidylinositol (GPI)-anchored surface proteins was screened for virulence phenotypes in vitro. During the screening, overexpression of IFF4 was found to increase the adherence of C. albicans to plastic and to human epithelial cells, but not endothelial cells. Consistent with the in vitro results, IFF4 overexpression modestly increased the tissue fungal burden during murine vaginal candidiasis. In addition to the in vitro screening tests, IFF4 overexpression was found to increase C. albicans susceptibility to neutrophil-mediated killing. Furthermore, IFF4 overexpression decreased the severity of hematogenously disseminated candidiasis in normal mice, but not in neutropenic mice, again consistent with the in vitro phenotype. Overexpression of 12 other GPI proteins did not affect normal GPI protein cell surface accumulation, demonstrating that the overexpression strategy did not affect the cell capacity for making such proteins. These data indicate that the same gene can increase or decrease candidal virulence in distinct models of infection, emphasizing the importance of studying virulence genes in different anatomical contexts. Finally, these data validate the use of a conditional overexpression/suppression genetic strategy to identify candidal virulence factors.


1995 ◽  
Vol 14 (3) ◽  
pp. 303-311 ◽  
Author(s):  
G C Inglis ◽  
C J Kenyon ◽  
C Szpirer ◽  
K Klinga-Levan ◽  
R G Sutcliffe ◽  
...  

ABSTRACT Mouse hepatoma × rat hepatocyte hybrids that segregate rat chromosomes were used to determine the chromosomal location of the rat genes encoding 11 β-hydroxylase and aldosterone synthase (Cyp11b1 and Cyp11b2 respectively). By means of species-specific restriction fragments and microsatellite markers both genes were mapped to rat chromosome 7. The Cyp11b1 microsatellite marker was subsequently found to vary in length between and within rat strains. Furthermore, we compared the sequences of Cyp11b1 markers in two genetically hypertensive strains of rat with their normotensive counterparts. Previous studies have indicated that 11β-hydroxylase activities in Milan and Lyon hypertensive strains are different from their respective genetic controls. The Cyp11b1 microsatellite regions from Lyon hypotensive and normotensive strains of rat were similar and were both shorter by 15 bases than that of the Lyon hypertensive strain. The Cyp11b1 marker in Milan hypertensive (MHS) and normotensive (MNS) strains differ from all the Lyon strains and from each other. The MHS marker is 12 bases shorter than that of MNS rats. These differences in microsatellite length may provide useful polymorphic markers in co-segregation studies of genetic hypertension in rats.


2020 ◽  
Author(s):  
Xu Lin ◽  
Hong-Mei Xiao ◽  
Hui-Min Liu ◽  
Wan-Qiang Lv ◽  
Jonathan Greenbaum ◽  
...  

AbstractAlthough gut microbiota influences osteoporosis risk, the individual species involved, and underlying mechanisms, are unknown. We performed integrative analyses in a Chinese cohort with metagenomics/targeted metabolomics/whole-genome sequencing. Bacteroides vulgatus was found negatively associated with bone mineral density (BMD), this association was validated in US Caucasians. Serum valeric acid was positively associated with BMD, and B.vulgatus causally downregulated it. Ovariectomized mice fed B.vulgatus had decreased bone formation and increased bone resorption, lower BMD and poorer bone micro-structure. Valeric acid suppressed NF-κB p65 protein production (pro-inflammatory), and enhanced IL-10 mRNA expression (anti-inflammatory), leading to suppressed maturation of osteoclast-like cells, and enhanced maturation of osteoblasts in vitro. B.vulgatus and valeric acid represent promising targets for osteoporosis prevention/treatment.


1999 ◽  
Vol 43 (8) ◽  
pp. 1968-1974 ◽  
Author(s):  
Karl W. Henry ◽  
M. Cristina Cruz ◽  
Santosh K. Katiyar ◽  
Thomas D. Edlind

ABSTRACT Antifungal azoles (e.g., fluconazole) are widely used for prophylaxis or treatment of Candida albicans infections in immunocompromised individuals, such as those with AIDS. These individuals are frequently treated with a variety of additional antimicrobial agents. Potential interactions between three azoles and 16 unrelated drugs (antiviral, antibacterial, antifungal, and antiprotozoal agents) were examined in vitro. Two compounds, tested at concentrations achievable in serum, demonstrated an antagonistic effect on azole activity against C. albicans. At fluconazole concentrations two to four times the 50% inhibitory concentration,C. albicans growth (relative to treatment with fluconazole alone) increased 3- to 18-fold in the presence of albendazole (2 μg/ml) or sulfadiazine (50 μg/ml). Antagonism (3- to 78-fold) of ketoconazole and itraconazole activity by these compounds was also observed. Since azole resistance has been correlated with overexpression of genes encoding efflux proteins, we hypothesized that antagonism results from drug-induced overexpression of these same genes. Indeed, brief incubation of C. albicans with albendazole or sulfadiazine resulted in a 3-to->10-fold increase in RNAs encoding multidrug transporter Cdr1p or Cdr2p. Zidovudine, trimethoprim, and isoniazid, which were not antagonistic with azoles, did not induce these RNAs. Fluphenazine, a known substrate for Cdr1p and Cdr2p, strongly induced their RNAs and, consistent with our hypothesis, strongly antagonized azole activity. Finally, antagonism was shown to require a functional Cdr1p. The possibility that azole activity against C. albicans is antagonized in vivo as well as in vitro in the presence of albendazole and sulfadiazine warrants investigation. Drug-induced overexpression of efflux proteins represents a new and potentially general mechanism for drug antagonism.


1998 ◽  
Vol 180 (18) ◽  
pp. 4775-4780 ◽  
Author(s):  
Jörg Deiwick ◽  
Thomas Nikolaus ◽  
Jaqueline E. Shea ◽  
Colin Gleeson ◽  
David W. Holden ◽  
...  

ABSTRACT The Salmonella typhimurium genome contains two pathogenicity islands (SPI) with genes encoding type III secretion systems for virulence proteins. SPI1 is required for the penetration of the epithelial layer of the intestine. SPI2 is important for the subsequent proliferation of bacteria in the spleens of infected hosts. Although most mutations in SPI2 lead to a strong reduction of virulence, they have different effects in vitro, with some mutants having significantly increased sensitivity to gentamicin and the antibacterial peptide polymyxin B. Previously we showed that certain mutations in SPI2 affect the ability of S. typhimurium to secrete SPI1 effector proteins and to invade cultured eukaryotic cells. In this study, we show that these SPI2 mutations affect the expression of the SPI1 invasion genes. Analysis of reporter fusions to various SPI1 genes reveals highly reduced expression of sipC,prgK, and hilA, the transcriptional activator of SPI1 genes. These observations indicate that the expression of one type III secretion system can be influenced dramatically by mutations in genes encoding a second type III secretion system in the same cell.


2020 ◽  
Vol 38 (No. 3) ◽  
pp. 137-143
Author(s):  
Michaela Rollová ◽  
Lucia Gharwalova ◽  
Aleš Krmela ◽  
Věra Schulzová ◽  
Jana Hajšlová ◽  
...  

The biological activity of polyphenol substances contained in food supplements prepared from Vitis vinifera can affect the microorganisms present in the digestive tract in terms of their representation and activity of the individual species. This study deals with resveratrol and two polyphenol-rich extracts (extract from V. vinifera canes and the commercial product Regrapex-R-forte) and their effect on selected gut microbiota (Bifidobacterium animalis subsp. lactis Bb-12, Lactobacillus acidophilus LA-5, Lactobacillus casei Lafti L-26, Citrobacter freundii DBM 3127, Escherichia coli DBM 3125). The effect of the studied agents on planktonic and biofilm growth of the microorganisms was determined as minimum inhibitory concentration (MIC80) and minimum biofilm inhibitory concentration (MBIC80), respectively. The extracts induced metabolic activity as well as total biofilm biomass production in probiotic strain L. acidophilus LA-5 while successfully inhibiting the growth of opportunistic pathogenic microorganisms C. freundii DBM 3127 and E. coli DBM 3125.


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