Frontiers | Selective Essential Oils from Spice or Culinary Herbs Have High Activity against Stationary Phase and Biofilm Borrelia burgdorferi | Medicine

 Although the majority of patients with acute Lyme disease can be cured with the standard 2–4 week antibiotic treatment, about 10–20% of patients continue suffering from chronic symptoms described as posttreatment Lyme disease syndrome. While the cause for this is debated, one possibility is that persister bacteria are not killed by the current Lyme antibiotics and remain active in the system. It has been reported that essential oils have antimicrobial activities and some have been used by patients with persisting Lyme disease symptoms. However, the activity of essential oils against the causative agent Borrelia burgdorferi (B. burgdorferi) has not been well studied. Here, we evaluated the activity of 34 essential oils against B. burgdorferi stationary phase culture as a model for persister bacteria. We found that not all essential oils had activity against the B. burgdorferi stationary phase culture, with top five essential oils (oregano, cinnamon bark, clove bud, citronella, and wintergreen) at a low concentration of 0.25% showing high anti-persister activity that is more active than the known persister drug daptomycin. Interestingly, some highly active essential oils were found to have excellent anti-biofilm ability as shown by their ability to dissolve the aggregated biofilm-like structures. The top three hits, oregano, cinnamon bark, and clove bud completely eradicated all viable cells without any regrowth in subculture in fresh medium, whereas but not citronella and wintergreen did not have this effect. Carvacrol was found to be the most active ingredient of oregano oil showing excellent activity against B. burgdorferi stationary phase cells, while other ingredients of oregano oil p-cymene and α-terpinene had no apparent activity. Future studies are needed to characterize and optimize the active essential oils in drug combination studies in vitro and in vivo and to address their safety and pharmacokinetic properties before they can be considered as a novel treatment of persistent Lyme disease."



'via Blog this'

Common antiseptic ingredients de-energize cells and impair hormone response

 "A new in-vitro study by University of California, Davis, researchers indicates that quaternary ammonium compounds, or "quats," used as antimicrobial agents in common household products inhibit mitochondria, the powerhouses of the cell, as well as estrogenic functions in cells. Their findings will appear online Aug. 22 in Environmental Health Perspectives, a publication of the National Institute of Environmental Health Sciences.

Quats are used as antiseptics in toothpastes, mouthwashes, lozenges, nasal sprays, eye drops, shampoos, lotions, intravaginal spermicidal sponges and household cleaners, to name a few.
"Disinfectants that we are putting on and in our bodies, and using in our environment, have been shown to inhibit mitochondrial energy production and the cellular estrogen response," said biochemist Gino Cortopassi in the UC Davis School of Veterinary Medicine. "This raises concern because exposure to other mitochondrial-inhibiting drugs, such as rotenone and MPTP, is associated with increased risk for Parkinson's disease.""



Paper:-

In Vitro Evaluation of Mitochondrial Function and Estrogen Signaling in Cell Lines Exposed to the Antiseptic Cetylpyridinium Chloride

DNA replication is the target for the antibacterial effects of nonsteroidal anti-inflammatory drugs.

 Evidence suggests that some nonsteroidal anti-inflammatory drugs (NSAIDs) possess antibacterial properties with an unknown mechanism. We describe the in vitro antibacterial properties of the NSAIDs carprofen, bromfenac, and vedaprofen, and show that these NSAIDs inhibit the Escherichia coli DNA polymerase III β subunit, an essential interaction hub that acts as a mobile tether on DNA for many essential partner proteins in DNA replication and repair. Crystal structures show that the three NSAIDs bind to the sliding clamp at a common binding site required for partner binding. Inhibition of interaction of the clamp loader and/or the replicative polymerase α subunit with the sliding clamp is demonstrated using an in vitro DNA replication assay. NSAIDs thus present promising lead scaffolds for novel antibacterial agents targeting the sliding clamp.

In vitro protective efficacy of Lithium chloride against Mycoplasma hyopneumoniae infection. - PubMed - NCBI

 Mycoplasma hyopneumoniae (M. hyopneumoniae) infection affects the swine industry. Lithium chloride (LiCl), is a drug used to treat bipolar disorder and has also shown activity against bacterial and viral infections. Herein, we evaluated the antibacterial activity of LiCl on PK-15 cells infected with M. hyopneumoniae. Incubation of LiCl (40mM) with cells for 24h, did not significantly affect the cell viability. The qRT-PCR showed ~80% reduction in M. hyopneumoniae genome when LiCl added post-infection. A direct effect of LiCl on bacteria was also observed. However, treatment of cells with LiCl prior infection, does not protect against the infection. Anti-bacterial activity of LiCl was further confirmed by IFA, which demonstrated a reduction in the bacterial protein. With 40mM LiCI, the apoptotic cell death, production of nitric oxide and superoxide anion induced by M. hyopneumoniae, were prevented by ~80%, 60% and 58% respectively. Moreover, caspase-3 activity was also reduced (82%) in cells treated with 40mM LiCl. LiCl showed activity against various strains of M. hyopneumoniae examined in our study. Collectively, our data showed that LiCl inhibited the infection of M. hyopneumoniae through anti-apoptotic mechanism.

Sweet taste receptors are primary sentinels in defense against bacterial infections in the upper airway, study finds

Scientists from the Perelman School of Medicine at the University of Pennsylvania reveal that the release of antimicrobial peptides is partially controlled by bitter taste receptors in the upper airway on a cell previously identified in animals and only recently in humans known as solitary chemosensory cells (SCCs). What's more, the action of the bitter receptors is blocked when sweet taste receptors are stimulated by sugars such as glucose. This study, published online ahead of print in the Journal of Clinical Investigation, suggests that sweet taste receptors expressed on SCCs in the upper
airway sense bacterial overgrowth and, in turn, control the release of AMPs.

SFN Transgenic Caenorhabditis elegans and transfected cultured cells expressing human Abeta resist infection by salmonella typhimurium

 Our laboratory recently reported that synthetic Abeta peptide has in vitro antimicrobial activity against at least six human pathogens. More recently we presented data suggesting Abeta binding and antimicrobial activity against pathogenic forms of Candida albicans is increased 2-3 orders of magnitude by oligomerization. In this study we present data on the in vivo efficacy of soluble oligomeric Abeta as a protective antimicrobial peptide (AMP). Experiments used cultured transfected cell monolayers and transgenic (Tg) Caenorhabditis elegans as host models and the intracellular bacterial pathogen Salmonella typhimurium as the infecting agent. Data is consistent with a in vivo role for Abeta as an AMP.
METHODS;
Abeta-mediated protection was first tested in a cultured cell monolayer model. Monolayers of naive or transfected cells expressing the 42 residue Abeta isoform (Abeta42) were prepared and infected with S. typhimurium bacteria labeled with red fluorescent protein (Salmonella-RFP) using the gentamycin infection assay protocol. Experiments next characterized resistance to Salmonella-RFP infection in a C. Elegans model. Infection of CL2122 control worms expressing green fluorescent protein (GFP) alone was compared to GMC101 Tg animals co-expressing GFP and Abeta42. Infection in both models was monitored using confocal microscopy, and viability, behavioral and biochemical assays. Experiments included immunochemical and chromatographic characterization of the oligomerization state of Abeta in host models.
RESULTS;
For cultured cells Abeta42 expression was associated with a 1-2 order of magnitude reduction in Salmonella invasion. In addition, survival of transfection Abeta expressing cells was significantly extended compared to naive cells. In the C. elegans infection model the spread of Salmonella-RFP was significantly inhibited in Abeta42 expressing tissues while overall bacterial load was significantly lower for GMC101 Tg worms compared to the CL2122 control strain. Biochemical data was consistent with an Abeta oligomer mediated antimicrobial mechanism.
CONCLUSION; Data is consistent with our previous findings of a potent in vitro antimicrobial activity for Abeta. The new finding confirm that expression of Abeta is also protective against invasive bacterial pathogens in vivo in cultured cells and C. elegans host models. Our data is further evidence that Abeta is an AMP and normally functions as part of the brains innate immune system.

SFN:Antimicrobial activity of soluble Aβ oligomers is mediated by the VHHQKL heparin-binding domain

 The β-amyloid protein (Aβ) plays a key role in the pathogenesis of Alzheimer's disease. The Aβ peptide sequence includes a VHHQKL heparin-binding domain. Although pathological activities mediated by Aβ’s VHHQKL domain have been extensively investigated, a normal physiological function has not been proposed for the peptide’s apparent affinity for sugars. We recently presented data consistent with a role for Aβ as an antimicrobial peptide (AMP). Our most recent data show picomolar concentrations of soluble Aβ oligomers have potent in vitro antimicrobial activities that appear to be mediated by the heparin-binding VHHQKL domain. Previous studies demonstrate binding of microbial cell-wall carbohydrates plays a key role in the antimicrobial function the archetypal AMP LL-37, which shares the same XBBXBX heparin-binding motif as Aβ. Here we present data characterizing the role of Aβ’s heparin-binding domain in context of the peptide’s AMP activities. 
METHODS: Experiments first characterized the binding of monomeric and oligomeric Aβ to host and microbial carbohydrates using ELISA and chromatographic assays. Aβ’s anti-adhesion and agglutination activities against pathogenic forms of Candida albicans were then characterized in a cell culture monolayer infection model. Yeast aggregates were also analyzed for markers of β-amyloid fibrils. Experiments included the heparin-binding AMP LL-37 as a control. 
RESULTS: Aβ oligomers bound microbial polysaccharides in in vitro binding assays. Affinity of soluble, cell-secreted oligomeric Aβ was two-to-three orders of magnitude higher than synthetic monomeric peptide. Deglycosylation of Candida cells attenuated Aβ binding. Microbial sugars that specifically block the actions of heparin-binding AMPs ablated Aβ’s anti-adhesion and agglutination activities in cell culture. Analysis ofCandida aggregates suggests agglutination involves entrapment of yeast cells by β-amyloid fibrils.
CONCLUSIONS: Data is consistent with protective antimicrobial activity for Aβ oligomers mediated by the heparin-binding VHHQKL domain. Findings suggest the normal target sugars for Aβ are not host structural carbohydrates but rather microbial cell-wall polysaccharides. Based on our new data, we propose a three-part mechanism for Aβ antimicrobial activity. Aβ oligomers first bind to microbial cell walls via the heparin-binding VHHQKL domain. Bound Aβ oligomers interfere with the normal adhesion of microbial cells to host tissues. Lastly, resulting planktonic microbial cells are agglutinated by β-amyloid fibrils that are seeded by bound peptide and grow through recruitment of free Aβ oligomers.

Platelets Help Tackle Bacteria | The Scientist Magazine®

 Platelets may contribute to protection against bacterial infection, according to new research published today (June 16) in Nature Immunology. Scientists found that in the livers of mice, platelets collaborated with specialized white blood cells to capture and engulf blood-borne bacteria, and this interaction helped protect the animals from bacterial infection.

ScienceDirect.com - Virology - What is needed for phage therapy to become a reality in Western medicine?

B0007272 Bacteriophage (Photo credit: wellcome images)

The current status of phage therapy approaches is reviewed and possible hurdles to a practical medical application of bacteriophages in Western countries are identified as discussed at a recent EMBO meeting on “Viruses of Microbes” in Brussels. In view of the growing antibiotic resistance crisis, a coordinated effort by the public health sector is needed to evaluate the potential of phage therapy as an adjunct to antibiotics.

Now we know why old schizophrenia medicine works on antibiotics-resistant bacteria

Thioridazine is known to possess antibacterial effects, although it was not clear how this worked............ "When we treat the bacteria with antibiotics alone, nothing happens -- the bacteria are not even affected. But when we add both thioridazine and antibiotics, something happens: thioridazine weakens the bacterial cell wall by removing glycine (an amino acid) from the cell wall. In the absence of glycine, the antibiotics can attack the weakened cell wall and kill staphylococcus bacteria," explains Janne Kudsk Klitgaard, visiting scholar at the Department of Biochemistry and Molecular Biology, University of Southern Denmark".

Related articles

• Pimozide Inhibits the AcrAB-TolC Efflux Pump in Escherichia coli.
• 
  
• Activity of trifluoperazine against replicating, non-replicating and drug resistant M. tuberculosis.
• 
  

Evidence of significant synergism between antibiotics and the antipsychoticantimicrobial drug flupenthixol.

Evaluation of five antischizophrenic agentsagainst Toxoplasmagondiiin human cell cultures.

Clinical potential of minocyclineschizophrenia

Researchers discover endogenous antibiotic in the brain

"Scientists from the Luxembourg Centre for Systems Biomedicine (LCSB) of the University of Luxembourg have discovered that immune cells in the brain can produce a substance that prevents bacterial growth: namely itaconic acid. Until now, biologists had assumed that only certain fungi produced itaconic acid. A team working with Dr. Karsten Hiller, head of the Metabolomics Group at LCSB, and Dr. Alessandro Michelucci has now shown that even so-called microglial cells in mammals are also capable of producing this acid."

Promising new antibiotic targets potentially deadly gut infections

Researchers at the University of Virginia School of Medicine have developed a promising new antibiotic to treat potentially deadly gastrointestinal infections without harming the beneficial probiotic bacteria that help prevent relapse.The investigational drug, Amixicile, can take down even hyper-virulent strains of drug-resistant Clostridium difficile – commonly called "C. diff" – which kills 14,000 Americans each year. It also shows efficacy against Cryptosporidium (protozoans that cause diarrhea) and Helicobacter pylori in mouse models of infection and potentially against many other human pathogens, including Campylobacter jejuni. 

Infection biology: The elusive third factor

LMU researchers have identified an enzyme that is involved in a modification pathway that is essential for bacterial pathogenicity. Because it shows no similarity to other known proteins, it may be an ideal target for development of novel antimicrobial drugs.

Antibacterials in personal-care products linked to allergy risk in children

(Medical Xpress) -- Exposure to common antibacterial chemicals and preservatives found in soap, toothpaste, mouthwash and other personal-care products may make children more prone to a wide range of food and environmental allergies, according to new research from Johns Hopkins Children’s Center.The investigators say their findings are also consistent with the so-called hygiene hypothesis, which has recently gained traction as one possible explanation behind the growing rates of food and environmental allergies in the developed world.