Environmental metals can be noxious to the surrounding biota, indirectly impact freshwater habitats, and also impact microbiological communities. In this study, zinc (Zn) (55.5 mg/kg), manganese (Mn) ...(863.4 mg/kg) and lead (Pb) (17.5 mg/kg) levels measured in Houston watershed flood plain soil samples were higher than environmental agencies’ thresholds. To investigate the effects of metal exposures, an environmentally isolated Serratia marcescens (SME), etiological agent of endocarditis and respiratory infections, and its reference strain (SMR) were exposed to Pb, Zn, and Mn, and subsequent oxidative stress responses and biofilm production were measured. Not surprisingly, SME was less sensitive to all 3 metal exposures than was SMR. Interestingly, SME produced increased biofilm and was more resistant to oxidative stress in the presence of Zn and Pb than SMR. In a 6 h lung infection model using BAES-2B cells, SME exhibited greater proliferation than SMR in all metal challenges. Similarly, in our HT29 gut infection model, SME out-proliferated SMR when challenged with Pb and Mn following the 6 h infection. Taken together, SME was better able to withstand environmental stressors than SMR, suggesting increased virulence potential of this opportunistic human pathogen.
•Zn (55.5 mg/kg), Mn (863.4 mg/kg) and Pb (17.5 mg/kg) Houston soil levels exceeded environmental agencies’ thresholds.•Environmental S. marcescens produced increased biofilm and increased oxidative-stress resistance in the presence of Zn and Pb.•In gut and lung co-culture infections, the environmentally isolated S. marcescens exhibited increased virulence potential.
Guggulsterone for Chemoprevention of Cancer Shishodia, Shishir; Azu, Nkem; Rosenzweig, Jason A ...
Current pharmaceutical design,
01/2016, Letnik:
22, Številka:
3
Journal Article
Recenzirano
Guggulsterone 4, 17(20)-pregnadiene-3, 16-dione is a plant sterol derived from the gum resin of the tree Commiphora wightii. The gum resin of the guggul tree has been used in traditional medicine for ...centuries to treat obesity, liver disorders, internal tumors, malignant sores, ulcers, urinary complaints, intestinal worms, leucoderma, sinus, edema and sudden paralytic seizures. Guggulsterone has been shown to modulate the nuclear receptors, farnesoid X receptor, pregnane X receptor, CYP 2b10 gene expression, and the bile salt export pump for cholesterol elimination. Recent research indicates that the active components of gum guggul, E- and Zguggulsterone have the potential to both prevent and treat cancers. Guggulsterone inhibits the growth of a wide variety of tumor cells and induces apoptosis through down regulation of antiapoptotic gene products (IAP1, xIAP, Bfl-1/A1, Bcl-2, cFLIP, and survivin), modulation of cell cycle proteins (cyclin D1 and c-Myc), activation of caspases, inhibition of Akt, and activation of JNK. Guggulsterone modulates the expression of gene products involved in metastasis (MMP-9, COX-2, and VEGF) of tumor cells. Guggulsterone mediates gene expression through the modulation of several transcription factors, including NF-κB, STAT3, C/EBPα, androgen receptor, and glucocorticoid receptors. This review describes the anti-cancer properties, molecular targets, and the apoptotic effects of guggulsterone.
Aeromonas
species (spp.) are well-known fish pathogens, several of which have been recognized as emerging human pathogens. The organism is capable of causing a wide spectrum of diseases in humans, ...ranging from gastroenteritis, wound infections, and septicemia to devastating necrotizing fasciitis. The systemic form of infection is often fatal, particularly in patients with underlying chronic diseases. Indeed, recent trends demonstrate rising numbers of hospital-acquired
Aeromonas
infections, especially in immuno-compromised individuals. Additionally,
Aeromonas
-associated antibiotic resistance is an increasing challenge in combating both fish and human infections. The acquisition of antibiotic resistance is related to
Aeromonas
’ innate transformative properties including its ability to share plasmids and integron-related gene cassettes between species and with the environment. As a result, alternatives to antibiotic treatments are desperately needed. In that vein, many treatments have been proposed and studied extensively in the fish-farming industry, including treatments that target
Aeromonas
quorum sensing. In this review, we discuss current strategies targeting quorum sensing inhibition and propose that such studies empower the development of novel chemotherapeutic approaches to combat drug-resistant
Aeromonas
spp. infections in humans.
Key points
• Aeromonas notoriously acquires and maintains antimicrobial resistance, making treatment options limited.
• Quorum sensing is an essential virulence mechanism in Aeromonas infections.
• Inhibiting quorum sensing can be an effective strategy in combating Aeromonas infections in animals and humans.
As the reality of pandemic threats challenges humanity, exemplified during the ongoing SARS-CoV-2 infections, the development of vaccines targeting these etiological agents of disease has become ...increasingly critical. Of paramount concern are novel and reemerging pathogens that could trigger such events, including the plague bacterium
Yersinia pestis
.
Y. pestis
is responsible for more human deaths than any other known pathogen and exists globally in endemic regions of the world, including the four corners region and Northern California in the USA. Recent cases have been scattered throughout the world, including China and the USA, with serious outbreaks in Madagascar during 2008, 2013–2014, and, most recently, 2017–2018. This review will focus on recent advances in plague vaccine development, a seemingly necessary endeavor, as there is no Food and Drug Administration–licensed vaccine available for human distribution in western nations, and that antibiotic-resistant strains are recovered clinically or intentionally developed. Progress and recent development involving subunit, live-attenuated, and nucleic acid–based plague vaccine candidates will be discussed in this review.
Key points
•
Plague vaccine development remains elusive yet critical.
•
DNA, animal, and live-attenuated vaccine candidates gain traction.
Houston watersheds are susceptible to microbial contamination as well as chemical contaminations from bordering industrial facilities. Bacterial loads in various Houston bayous were determined, and ...pathogenic Gram-negative bacteria were isolated for characterization. Isolates included Klebsiella aerogenes and Klebsiella pneumoniae. To determine whether environmental exposures to lead (Pb), measured in our Houston bayou samples, resulted in bacterial adaptations, we compared growth kinetics, biofilm production, oxidative stress resistance, and eukaryotic co-culture growth of environmentally isolated K. aerogenes and K. pneumoniae to their respective commercially acquired reference strains. Interestingly, the K. aerogenes environmental isolate displayed significantly better growth than the reference strain in the presence of 50 ppb of Pb. Unexpectedly, we did not observe any differences in biofilm production of the aforementioned strains when challenged with a range of Pb (0.5–50 ppb). However, when comparing our K. pneumoniae environmental isolate to its reference strain, there were significantly higher levels of biofilm produced by the environmental isolate when challenged with Pb concentrations of 10 and 50 ppb. When grown in eukaryotic cell co-culture with either BAES 2B lung cells or CCD 841 colon epithelial cells in the presence of 20 ppb Pb, the environmental isolates of K. aerogenes and K. pneumoniae had a significantly higher fold-increase over 6 h than their respective reference strains. Taken together, the environmentally isolated Klebsiella spp. appeared to be more Pb-tolerant than their respective reference strains, a possible environmental adaptation. Such enhanced tolerance can promote environmental persistence and increase the possibility of causing human disease.
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•Mustang Bayou had elevated Pb levels as well as the greatest bacterial loads.•Klebsiella isolated from Houston area bayous had increased antibiotic resistance.•Pb levels measured in Houston bayous in 2018 were between 0.28 and 11.5 ppb.•Pb-exposed Klebsiella pneumoniae produced more biofilm than its reference strain.•Pb-exposed Klebsiella spp. proliferated better in lung and gut cell co-culture.
For unsuspecting bacteria, the difference between life and death depends upon efficient and specific responses to various stressors. Facing a much larger world, microbes are invariably challenged ...with ever-changing environments where temperature, pH, chemicals, and nutrients are in a constant state of flux. Only those that are able to rapidly reprogram themselves and express subsets of genes needed to overcome the stress will survive and outcompete neighboring microbes. Recently, low shear stress, emulating microgravity (MG) experienced in space, has been characterized in a number of microorganisms including fungi and prokaryotes ranging from harmless surrogate organisms to bona fide pathogens. Interestingly, MG appears to induce a plethora of effects ranging from enhanced pathogenicity in several Gram-negative enterics to enhanced biofilm formation. Furthermore, MG-exposed bacteria appeared better able to handle subsequent stressors including: osmolarity, pH, temperature, and antimicrobial challenge while yeast exhibited aberrant budding post-MG-exposure. This review will focus on MG-induced alterations of virulence in various microbes with the emphasis placed on bacteria.
Recent studies evaluated the impact of dust exposure on pure and mixed cultures of
Escherichia coli
,
Enterococcus faecalis
,
Klebsiella pneumoniae
, and
Pseudomonas aeruginosa
, revealing increased ...biofilm formation and altered sensitivities to H
2
O
2
. In this study, we examined the impact of lead (Pb), house, road, and combined dust on
K. pneumoniae
and
P. aeruginosa
in pure, mixed, or eukaryotic co-culture with human alveolar basal epithelial (A549) cells. Although no impact on pure or mixed culture growth was observed when bacteria were exposed to Pb, house, or road dust, increased biofilm was produced by
P. aeruginosa
in the presence of 0.8 μg/mL of Pb, while
P. aeruginosa
and
K. pneumoniae
both exhibited increased biofilm production in the presence of 100 μg/mL of house, road, and combined dust. When co-cultured with eukaryotic A549 cells, both bacteria demonstrated increased proliferation 6 h post-infection when challenged with house, road, or combined dust. However, when mixed bacteria were co-cultured with A549 cells,
P. aeruginosa
exhibited a significant ~ 1.5-fold increased proliferation in the presence of 100 μg/mL house, road, or combined dust. In sharp contrast,
K. pneumoniae
exhibited significantly reduced proliferation, when in mixed (with
P. aeruginosa
) A-549 co-culture, following exposure to 100 μg/mL house, road, or combined dust. To evaluate whether a host cell inflammatory response contributed to this disparity, NF-κB activation was evaluated in each co-culture infection.
K. pneumoniae
-A-549 co-culture, treated with 100 μg/mL of combined dust, exhibited no alterations in NF-κB translocation to the nucleus. Further, no differences in cytokine production were observed in the
K. pneumoniae
A-549 co-culture treated with 100 μg/mL of house dust. Taken together, these data suggest that within the lung environment, mixed infections exposed to dust or dust contaminants could benefit one organism at the expense of the other, independent of the activation of inflammatory pathways.
On a daily basis, humans, and their colonizing microbiome, are exposed to both indoor and outdoor dust, containing both deleterious organic and inorganic contaminants, through dermal contact, ...inhalation, and ingestion. Recent studies evaluating the dust exposure responses of opportunistic pathogens, such as
Escherichia coli
and
Pseudomonas aeruginosa
, revealed significant increases in biofilm formation following dust exposure. In this study, the effects of dust exposure on mixed bacterial cultures as well as HT-29 co-cultures were evaluated. As it was observed in pure, single bacterial cultures earlier, neither indoor nor outdoor dust exposure (at concentrations of 100 μg/mL) influenced the growth of mixed bacterial liquid cultures. However, when in paired mixed cultures, dust exposure increased sensitivity to oxidative stress and significantly enhanced biofilm formation (outdoor dust). More specifically, mixed cultures (
E. coli
-
Klebsiella pneumoniae
,
K. pneumoniae
-
P. aeruginosa
, and
E. coli
-
P. aeruginosa
) exhibited increased sensitivity to 20 and 50 mM of H
2
O
2
in comparison to their pure, single bacterial culture counterparts and significantly enhanced biofilm production for each mixed culture. Finally, bacterial proliferation during a eukaryotic gut cell (HT29) co-culture was significantly more robust for both
K. pneumoniae
and
P. aeruginosa
when exposed to both house and road dust; however,
E. coli
only experienced significantly enhanced proliferation, in HT29 co-culture, when exposed to road dust. Taken together, our findings demonstrate that bacteria respond to dust exposure differently when in the presence of multiple bacterial species or when in the presence of human gut epithelial cells, than when grown in isolation.
As their environments change, microbes experience various threats and stressors, and in the hypercompetitive microbial world, dynamism and the ability to rapidly respond to such changes allow ...microbes to outcompete their nutrient-seeking neighbors. Viewed in that light, the very difference between microbial life and death depends on effective stress response mechanisms. In addition to the more commonly studied temperature, nutritional, and chemical stressors, research has begun to characterize microbial responses to physical stress, namely low-shear stress. In fact, microbial responses to low-shear modeled microgravity (LSMMG), which emulates the microgravity experienced in space, have been studied quite widely in both prokaryotes and eukaryotes. Interestingly, LSMMG-induced changes in the virulence potential of several Gram-negative enteric bacteria, e.g., an increased enterotoxigenic Escherichia coli-mediated fluid secretion in ligated ileal loops of mice, an increased adherent invasive E. coli-mediated infectivity of Caco-2 cells, an increased Salmonella typhimurium-mediated invasion of both epithelial and macrophage cells, and S. typhimurium hypervirulence phenotype in BALB/c mice when infected by the intraperitoneal route. Although these were some examples where virulence of the bacteria was increased, there are instances where organisms became less virulent under LSMMG, e.g., hypovirulence of Yersinia pestis in cell culture infections and hypovirulence of methicillin-resistant Staphylococcus aureus, Enterococcus faecalis, and Listeria monocytogenes in a Caenorhabditis elegans infection model. In general, a number of LSMMG-exposed bacteria (but not all) seemed better equipped to handle subsequent stressors such as osmotic shock, acid shock, heat shock, and exposure to chemotherapeutics. This mini-review primarily discusses both LSMMG-induced as well as bona fide spaceflight-specific alterations in bacterial virulence potential, demonstrating that pathogens’ responses to low-shear forces vary dramatically. Ultimately, a careful characterization of numerous bacterial pathogens’ responses to low-shear forces is necessary to evaluate a more complete picture of how this physical stress impacts bacterial virulence since a “one-size-fits-all” response is clearly not the case.
Within the last decade, many studies have highlighted the radical changes in the components of indoor and outdoor dust. For example, agents like automobile emitted platinum group elements and ...different kinds of organic phthalates and esters have been reported to be accumulating in the biosphere. Humans consistently face dermal, respiratory, and dietary exposures to these particles while indoors and outdoors. In fact, dust particulate matter has been associated with close to 500,000 deaths per year in Europe and about 200,000 deaths per year in the United States. To date, there has been limited examination of the physiological impact of indoor and outdoor dust exposure on normal flora microbes. In this study, the effect of indoor- and outdoor-dust exposure on three opportunistic bacterial species (Escherichia coli, Enterococcus faecalis, and Pseudomonas aeruginosa) was assessed. Specifically, bacterial growth, oxidative stress resistance, and biofilm production were measured following indoor- and outdoor-dust exposures. Studies were conducted in nutritionally-rich and -poor environments typically encountered by bacteria. Surprisingly, indoor-dust (200μg/mL), enhanced the growth of all three bacterial species in nutrient-poor conditions, but slowed growth in nutrient-rich conditions. In nutrient-rich medium, 100μg/mL exposure of either indoor- or outdoor-dust resulted in significantly reduced oxidative stress resistance in E. coli. Most interestingly, dust (indoor and outdoor), either in nutrient-rich or -poor conditions, significantly increased biofilm production in all three bacterial species. These data suggest that indoor and outdoor dust, can modify opportunistic bacteria through altering growth, sensitivity to oxidative stress, and their virulence potential through enhanced biofilm formation.
Display omitted
•indoor-dust enhanced bacterial growth in nutrient-poor medium•indoor dust slowed bacterial growth in nutrient-rich medium•exposure to dust significantly reduced E. coli’s oxidative stress resistance•dust exposure increased biofilm production in all 3 species•dust exposure influences bacterial growth, oxidative stress resistance, and virulence potential
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