bacterial density
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PLoS Genetics ◽  
2022 ◽  
Vol 18 (1) ◽  
pp. e1009992
Author(s):  
Shivohum Bahuguna ◽  
Magda Atilano ◽  
Marcus Glittenberg ◽  
Dohun Lee ◽  
Srishti Arora ◽  
...  

The gut sets the immune and metabolic parameters for the survival of commensal bacteria. We report that in Drosophila, deficiency in bacterial recognition upstream of Toll/NF-κB signalling resulted in reduced density and diversity of gut bacteria. Translational regulation factor 4E-BP, a transcriptional target of Toll/NF-κB, mediated this host-bacteriome interaction. In healthy flies, Toll activated 4E-BP, which enabled fat catabolism, which resulted in sustaining of the bacteriome. The presence of gut bacteria kept Toll signalling activity thus ensuring the feedback loop of their own preservation. When Toll activity was absent, TOR-mediated suppression of 4E-BP made fat resources inaccessible and this correlated with loss of intestinal bacterial density. This could be overcome by genetic or pharmacological inhibition of TOR, which restored bacterial density. Our results give insights into how an animal integrates immune sensing and metabolism to maintain indigenous bacteria in a healthy gut.


Microbiome ◽  
2022 ◽  
Vol 10 (1) ◽  
Author(s):  
Rishi Chanderraj ◽  
Christopher A. Brown ◽  
Kevin Hinkle ◽  
Nicole Falkowski ◽  
Robert J. Woods ◽  
...  

Abstract Background In ecology, population density is a key feature of community analysis. Yet in studies of the gut microbiome, bacterial density is rarely reported. Studies of hospitalized patients commonly use rectal swabs for microbiome analysis, yet variation in their bacterial density—and the clinical and methodologic significance of this variation—remains undetermined. We used an ultra-sensitive quantification approach—droplet digital PCR (ddPCR)—to quantify bacterial density in rectal swabs from 118 hospitalized patients. We compared bacterial density with bacterial community composition (via 16S rRNA amplicon sequencing) and clinical data to determine if variation in bacterial density has methodological, clinical, and prognostic significance. Results Bacterial density in rectal swab specimens was highly variable, spanning five orders of magnitude (1.2 × 104–3.2 × 109 16S rRNA gene copies/sample). Low bacterial density was strongly correlated with the detection of sequencing contamination (Spearman ρ = − 0.95, p < 10−16). Low-density rectal swab communities were dominated by peri-rectal skin bacteria and sequencing contaminants (p < 0.01), suggesting that some variation in bacterial density is explained by sampling variation. Yet bacterial density was also associated with important clinical exposures, conditions, and outcomes. Bacterial density was lower among patients who had received piperacillin-tazobactam (p = 0.017) and increased among patients with multiple medical comorbidities (Charlson score, p = 0.0040) and advanced age (p = 0.043). Bacterial density at the time of hospital admission was independently associated with subsequent extraintestinal infection (p = 0.0028), even when controlled for severity of illness and comorbidities. Conclusions The bacterial density of rectal swabs is highly variable, and this variability is of methodological, clinical, and prognostic significance. Microbiome studies using rectal swabs are vulnerable to sequencing contamination and should include appropriate negative sequencing controls. Among hospitalized patients, gut bacterial density is associated with clinical exposures (antibiotics, comorbidities) and independently predicts infection risk. Bacterial density is an important and under-studied feature of gut microbiome community analysis.


AMB Express ◽  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Soudabeh Ghodsi ◽  
Ali Esrafili ◽  
Hamid Reza Sobhi ◽  
Roshanak Rezaei Kalantary ◽  
Mitra Gholami ◽  
...  

AbstractContamination of water with bacteria is one of the main causes of waterborne diseases. The photocatalytic method on the basis of bacterial inactivation seems to be a suitable disinfectant due to the lack of by-products formation. Herein, g-C3N4/Fe3O4/Ag nanocomposite combined with UV-light irradiation was applied for the inactivation two well-known bacteria namely, E. coli and B. subtilis. The nanocomposite was prepared by a hydrothermal method, and subsequently it was characterized by XRD, FT-IR, SEM, EDX and PL analyses. The optimum conditions established for the inactivation of both bacteria were as follows: nanocomposite dosage 3 g/L and bacterial density of 103 CFU/mL. In the meantime, the efficient inactivation of E. coli and B. subtilis took 30 and 150 min, respectively. The results also revealed that inactivation rate dropped with an increase in the bacterial density. It is also pointed out that OH˚ was found out to be the main radical species involved in the inactivation process. Finally, the kinetic results indicated that the inactivation of E. coli and B. subtilis followed the Weibull model. It is concluded that C3N4/Fe3O4/Ag nanocomposite along with UV-light irradiation is highly effective in inactivating E. coli and B. subtilis bacteria in the aqueous solutions.


2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S443-S444
Author(s):  
Ruhmazia Khan ◽  
Zeel Shah ◽  
Vanthida Huang ◽  
Jaclyn Cusumano

Abstract Background Synergistic ampicillin plus ceftriaxone (AC) for Enterococcus faecalis infective endocarditis outpatient use is precluded by ampicillin’s poor room temperature stability. Penicillin has superior stability and has been combined with ceftriaxone (PC), however there is a lack of studies to demonstrate synergy. Methods AC and PC were evaluated, in duplicate, for synergy utilizing 24-hour in vitro time-kill assays with a starting inoculum of 106 colony forming units (CFU)/mL. Six clinical E. faecalis blood isolates and one wild-type E. faecalis isolate (JH2-2) were included. All isolates were susceptible to ampicillin and penicillin, with minimum inhibitory concentrations (MICs) ranging from 0.5-1 µg/mL and 2-4 µg/mL, respectively. Ampicillin and penicillin were tested at subinhibitory concentrations (0.25x and 0.5xMIC) as monotherapy and in combination with ceftriaxone average steady state concentrations for a dose of 2g IV q12hr (CPss 17.2 µg/mL), as all ceftriaxone MICs were high due to intrinsic resistance (MICs 128-2048 µg/mL). Synergy was defined as a ≥ 2 log10 decrease in CFU/mL at 24 hours from the most active single agent. Results An average increase in bacterial density from the starting inoculum was observed for all isolates against ampicillin 0.25xMIC alone, penicillin 0.25x and 0.5xMIC alone, and ceftriaxone alone (+1.60 ± 0.62, +1.91 ± 0.37, +1.48 ± 0.42, and +1.84 ± 0.46 log10 CFU/mL, respectively) [Table 1]. Ampicillin 0.5xMIC alone average increase in bacterial density from starting inoculum for all but two isolates (e2008 and e2009) was +1.21 ± 0.59 log10 CFU/mL. Isolates e2008 and e2009 were the only isolates with a higher penicillin MIC of 4 µg/mL, and did not display synergy for all AC and all PC combinations. AC synergy was observed for all other isolates, with only one isolate (e2012) displaying synergy at 0.5xMIC. PC synergy was observed for four isolates at 0.5xMIC (-3.47 ± 0.94 log10 CFU/mL) and for only one isolate (e2014) at 0.25xMIC but the change in bacterial density was -0.38 ± 0.24 log10 CFU/mL. Conclusion PC synergy against E. faecalis was observed with higher penicillin concentrations. AC and PC did not demonstrate synergy against isolates with a higher penicillin MIC of 4 µg/mL. Further research is warranted to better understand PC synergy against E. faecalis. Disclosures All Authors: No reported disclosures


Author(s):  
Andrew J Fratoni ◽  
David P Nicolau ◽  
Joseph L Kuti

Abstract Background Levofloxacin displays in vitro activity against Stenotrophomonas maltophilia (STM); however, current susceptibility breakpoints are supported by limited data. We employed the murine neutropenic thigh infection model to assess levofloxacin pharmacodynamics against STM. Methods Twenty-six clinical STM were studied using the neutropenic murine thigh infection model. Human simulated regimens (HSR) of levofloxacin 750 mg q24h were administered over 24 h. Efficacy was measured as the change in log10 cfu/thigh at 24 h compared with 0 h. Composite cfu data were fitted to an Emax model to determine the fAUC/MIC needed for stasis and 1 log10 reduction at 24 h. Monte Carlo simulation was performed to determine PTA. Results Levofloxacin MICs ranged from 0.5–8 mg/L. Mean bacterial burden at 0 h was 6.21 ± 0.20 log10 cfu/thigh. In the 24 h controls, bacterial growth was 1.64 ± 0.66 log10 cfu/thigh. In isolates with levofloxacin MICs ≤1, 2 and ≥4 mg/L, changes in bacterial density following levofloxacin HSR were −1.66 ± 0.89, 0.13 ± 0.97 and 1.54 ± 0.43 log10 cfu/thigh, respectively. The Emax model demonstrated strong agreement between fAUC/MIC and change in bacterial density (R2 = 0.82). The fAUC/MIC exposure needed for stasis and 1 log10 reduction was 39.9 and 54.9, respectively. PTAs for the 1 log10 reduction threshold were 95.8, 72.2, and 26.6% at MICs of 0.5, 1 and 2 mg/L, respectively. Conclusions These are the first data to describe fAUC/MIC thresholds predictive of cfu reductions for levofloxacin against STM. Due to poor in vivo efficacy and PTA at MICs ≥2 mg/L, reassessment of the current susceptibility breakpoint is warranted.


Author(s):  
Zina Alfahl ◽  
Gisli G. Einarsson ◽  
Katherine O’Neill ◽  
Deirdre F. Gilpin ◽  
J. Stuart Elborn ◽  
...  
Keyword(s):  

2021 ◽  
Author(s):  
Adi Wasis Prakosa ◽  
Muhammad Miftahussurur ◽  
Juniastuti Juniastuti ◽  
Langgeng Agung Waskito ◽  
Dalla Doohan ◽  
...  

2021 ◽  
Vol 8 ◽  
Author(s):  
Guangfu Zhao ◽  
Pan Li ◽  
Hao Mu ◽  
Nengzhang Li ◽  
Yuanyi Peng

Bovine Pasteurella multocida serogroup A (bovine PmA) is one of the most important pathogens causing fatal pneumonia in cattle. However, it is largely unknown how nutrition shapes bovine PmA infection. Here, we discovered that the infected lung held the highest bacterial density than other tissues during infection. By screening the different metabolites between high (lung)- and low (liver)-bacterial density tissues, the present work revealed that L-ascorbic acid and L-aspartic acid directly influenced bovine P. multocida growth. Interestingly, L-ascorbic acid, which is expressed at higher levels in the infected livers, inhibited bovine PmA growth as well as virulence factor expression and promoted macrophage bactericidal activity in vitro. In addition, ascorbic acid synthesis was repressed upon bovine PmA infection, and supplementation with exogenous L-ascorbic acid significantly reduced the bacterial burden of the infected lungs and mouse mortality. Collectively, our study has profiled the metabolite difference of the murine lung and liver during bovine PmA infection. The screened L-ascorbic acid showed repression of bovine PmA growth and virulence expression in vitro and supplementation could significantly increase the survival rate of mice and reduce the bacterial load in vivo, which implied that L-ascorbic acid could serve as a potential protective agent for bovine PmA infection in clinic.


2021 ◽  
Vol 27 ◽  
Author(s):  
Jewel Ju Ea Kim ◽  
Ildikó Kocsmár ◽  
György Miklós Buzás ◽  
Ildikó Szirtes ◽  
Orsolya Rusz ◽  
...  

The global rise in clarithromycin (Cla) resistance is considered to be the main contributor of Helicobacter pylori (Hp) eradication failures. In nearly half of the Cla-resistant Hp infections, Cla-susceptible bacteria are simultaneously present with the Cla-resistant ones (Cla-heteroresistance). The proportion of resistant bacteria in the bacterial population (R-fraction) and its predictive role for the use of Cla-based therapies in Cla-heteroresistant infections has not yet been investigated. Our retrospective study analyzed gastric biopsy samples of 62 Hp-positive patients with Cla-heteroresistant infection. Fluorescence In Situ Hybridization technique was used to visualize the coexistence of resistant and susceptible bacteria within one tissue sample. R-fraction was quantified on multichannel microimages by digital morphometry. Resistant bacteria had a patchy distribution within the whole bacterial population causing high diversity among the investigated areas. Patients were subdivided into two major groups according to whether a Cla-based eradication attempt was conducted before or after the biopsy sampling. R-fraction was significantly lower among cases having only one previous Cla-based eradication attempt vs. those that had multiple previous eradications, including at least one Cla-containing therapy (0.41 vs. 0.89, p = 0.0308). Majority of the patients without previous eradication attempt had successful eradication with Cla-containing regimen (59.26%), verified by a negative 13C-urea breath test or control biopsy. Multivariable model indicated that the therapeutic outcome using Cla-based regimens depended on the bacterial density rather than the R-fraction. Our study raises the potential use of Cla-containing eradication therapies in certain Cla-heteroresistant Hp infections, taking into account the possible predictive role of bacterial density.


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