scholarly journals INHIBITING PD-1 PATHWAY RESCUES PROTECTIVE IMMUNE RESPONSE IN TB PATIENTS: IMPACT ON BACILLARY EFFLUX PUMP AND MULTIDRUG-RESISTANCE TB

CHEST Journal ◽  
2021 ◽  
Vol 160 (4) ◽  
pp. A545
Author(s):  
Dipendra Mitra ◽  
Divya Kamboj ◽  
GOPIKA GUPTA ◽  
Girija Mehta ◽  
Sushmita Chakraborty ◽  
...  
Keyword(s):  
Immune Response ◽  
Multidrug Resistance ◽  
Efflux Pump ◽  
Protective Immune Response

scholarly journals Characterization of RarA, a Novel AraC Family Multidrug Resistance Regulator in Klebsiella pneumoniae

2012 ◽  
Vol 56 (8) ◽  
pp. 4450-4458 ◽  
Author(s):  
Mark Veleba ◽  
Paul G. Higgins ◽  
Gerardo Gonzalez ◽  
Harald Seifert ◽  
Thamarai Schneiders
Keyword(s):  
Multidrug Resistance ◽  
Klebsiella Pneumoniae ◽  
Efflux Pump ◽  
Content Type ◽  
Resistance Phenotype ◽  
Serratia Proteamaculans ◽  
Virulence Potential ◽  
Article Type ◽  
Acrab Efflux Pump

ABSTRACTTranscriptional regulators, such as SoxS, RamA, MarA, and Rob, which upregulate the AcrAB efflux pump, have been shown to be associated with multidrug resistance in clinically relevant Gram-negative bacteria. In addition to the multidrug resistance phenotype, these regulators have also been shown to play a role in the cellular metabolism and possibly the virulence potential of microbial cells. As such, the increased expression of these proteins is likely to cause pleiotropic phenotypes.Klebsiella pneumoniaeis a major nosocomial pathogen which can express the SoxS, MarA, Rob, and RamA proteins, and the accompanying paper shows that the increased transcription oframAis associated with tigecycline resistance (M. Veleba and T. Schneiders, Antimicrob. Agents Chemother. 56:4466–4467, 2012). Bioinformatic analyses of the availableKlebsiellagenome sequences show that an additional AraC-type regulator is encoded chromosomally. In this work, we characterize this novel AraC-type regulator, hereby called RarA (Regulator of antibiotic resistance A), which is encoded inK. pneumoniae,Enterobactersp. 638,Serratia proteamaculans568, andEnterobacter cloacae. We show that the overexpression ofrarAresults in a multidrug resistance phenotype which requires a functional AcrAB efflux pump but is independent of the other AraC regulators. Quantitative real-time PCR experiments show thatrarA(MGH 78578 KPN_02968) and its neighboring efflux pump operonoqxAB(KPN_02969_02970) are consistently upregulated in clinical isolates collected from various geographical locations (Chile, Turkey, and Germany). Our results suggest thatrarAoverexpression upregulates theoqxABefflux pump. Additionally, it appears thatoqxR, encoding a GntR-type regulator adjacent to theoqxABoperon, is able to downregulate the expression of theoqxABefflux pump, where OqxR complementation resulted in reductions to olaquindox MICs.

Variations in the protective immune response against streptococcal superantigens in populations of different ethnicity

2005 ◽  
Vol 195 (1) ◽  
pp. 37-43 ◽  
Author(s):  
Lily P. H. Yang ◽  
Björn K. G. Eriksson ◽  
Zinta Harrington ◽  
Nigel Curtis ◽  
Selwyn Lang ◽  
...  
Keyword(s):  
Immune Response ◽  
Protective Immune Response

scholarly journals Unexpected Link between Iron and Drug Resistance of Candida spp.: Iron Depletion Enhances Membrane Fluidity and Drug Diffusion, Leading to Drug-Susceptible Cells

2006 ◽  
Vol 50 (11) ◽  
pp. 3597-3606 ◽  
Author(s):  
Tulika Prasad ◽  
Aparna Chandra ◽  
Chinmay K. Mukhopadhyay ◽  
Rajendra Prasad
Keyword(s):  
Multidrug Resistance ◽  
Membrane Fluidity ◽  
Iron Uptake ◽  
Efflux Pump ◽  
Disulfonic Acid ◽  
Candida Spp ◽  
Copper Transporter ◽  
Iron Depletion ◽  
Cellular Iron ◽  
Increased Sensitivity

ABSTRACT Inthis study, we show that iron depletion in Candida albicans with bathophenanthrolene disulfonic acid and ferrozine as chelators enhanced its sensitivity to several drugs, including the most common antifungal, fluconazole (FLC). Several other species of Candida also displayed increased sensitivity to FLC because of iron restriction. Iron uptake mutations, namely,Δ ftr1 and Δftr2, as well as the copper transporter mutation Δccc2, which affects high-affinity iron uptake in Candida, produced increased sensitivity to FLC compared to that of the wild type. The effect of iron depletion on drug sensitivity appeared to be independent of the efflux pump proteins Cdr1p and Cdr2p. We found that iron deprivation led to lowering of membrane ergosterol by 15 to 30%. Subsequently, fluorescence polarization measurements also revealed that iron-restricted Candida cells displayed a 29 to 40% increase in membrane fluidity, resulting in enhanced passive diffusion of the drugs. Northern blot assays revealed that the ERG11 gene was considerably down regulated in iron-deprived cells, which might account for the lowered ergosterol content. Our results show a close relationship between cellular iron and drug susceptibilities of C. albicans. Considering that multidrug resistance is a manifestation of multifactorial phenomena, the influence of cellular iron on the drug susceptibilities of Candida suggests iron as yet another novel determinant of multidrug resistance.

Immunomodulation in host-protective immune response against murine tuberculosis through regulation of the T regulatory cell function

2015 ◽  
Vol 98 (5) ◽  
pp. 827-836 ◽  
Author(s):  
S. Das ◽  
K. Halder ◽  
A. Goswami ◽  
B. P. Chowdhury ◽  
N. K. Pal ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Function ◽  
Protective Immune Response ◽  
T Regulatory Cell ◽  
Regulatory Cell

Recombinant Glycoprotein B of Equine herpesvirus Type 1 Elicits Protective Immune Response against Challenge in BALB/c Mouse Model

2021 ◽  
Author(s):  
Alok Joshi ◽  
R.P. Gupta ◽  
Selvaraj Pavulraj ◽  
Bidhan Chandra Bera ◽  
Taruna Anand ◽  
...  
Keyword(s):  
Immune Response ◽  
Plasmid Dna ◽  
Protective Immune Response ◽  
Glycoprotein B ◽  
Equine Herpesvirus ◽  
Recombinant Glycoprotein ◽  
Herpesvirus Type ◽  
Equine Herpesvirus Type ◽  
Equine Herpesvirus Type 1

Background: Equine herpesvirus type 1 (EHV-1) is the most important viral pathogen of equines, causing respiratory illness, abortion, neonatal foal mortality and neurologic disorders. Large numbers of commercial EHV-1 vaccines are available to protect equines from the disease, but they provide only partial protection. Despite immunization with inactivated and modified live virus vaccine, mares show abortions. Present study was aimed to investigate the immunogenicity and protective efficacy of EHV-1 recombinant glycoprotein B (rgB) and gB expressing plasmid DNA against EHV-1 infection in BALB/c mice model.Methods: About 3-4 weeks old 225 female BALB/c mice were selected for the comparative study of immunization followed by challenged with EHV-1/India/Tohana/96-2 strain virus in 5 different groups of 45 animals each.Result: Following immunization, rgB vaccinated mice showed optimal stimulation of EHV-1 gB specific cell mediated and humoral mediated immunity (HMI and CMI). The gB expressing plasmid DNA vaccinated mice developed only CMI while inactivated whole virus vaccinated mice had only HMI. Upon EHV-1 challenge, all infected mice displayed variable levels of clinical signs with changes in body weight, however, vaccinated mice showed very rapid recovery with optimal protection. Positive control group mice showed severe pulmonary lesions along with persistence virus infection till 5 days post challenge (dpc) whereas vaccinated mice had less pulmonary lesion only up to 3dpc. Minimal lung lesions and early virus clearance was observed in the rgB immunized mice in comparison to the gB plasmid DNA and inactivated EHV-1 vaccine immunized mice. It has been concluded that immunization with rgB elicits optimum protective immune response against EHV-1 infection in mice model. The rgB could be a potential vaccine candidate against EHV-1 infection in equine in the future.

Sign in / Sign up

Export Citation Format

Share Document