scholarly journals Secretory System Components as Potential Prophylactic Targets for Bacterial Pathogens

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 892
Author(s):  
Wieslaw Swietnicki
Keyword(s):  
Small Molecules ◽  
Bacterial Infections ◽  
Bacterial Pathogens ◽  
Human Pathogens ◽  
Current Review ◽  
System Components ◽  
Secretory System

Bacterial secretory systems are essential for virulence in human pathogens. The systems have become a target of alternative antibacterial strategies based on small molecules and antibodies. Strategies to use components of the systems to design prophylactics have been less publicized despite vaccines being the preferred solution to dealing with bacterial infections. In the current review, strategies to design vaccines against selected pathogens are presented and connected to the biology of the system. The examples are given for Y. pestis, S. enterica, B. anthracis, S. flexneri, and other human pathogens, and discussed in terms of effectiveness and long-term protection.

scholarly journals Bacteriophages as drivers of bacterial virulence and their potential for biotechnological exploitation

2020 ◽  
Author(s):  
Kaat Schroven ◽  
Abram Aertsen ◽  
Rob Lavigne
Keyword(s):  
Small Molecules ◽  
Bacterial Infections ◽  
Bacterial Virulence ◽  
Arms Race ◽  
Control Mechanisms ◽  
Human Pathogens ◽  
Vaccine Candidates ◽  
Cargo Proteins ◽  
Genes Encoding ◽  
Mutualistic Relationship

ABSTRACT Bacteria-infecting viruses (phages) and their hosts maintain an ancient and complex relationship. Bacterial predation by lytic phages drives an ongoing phage-host arms race, whereas temperate phages initiate mutualistic relationships with their hosts upon lysogenization as prophages. In human pathogens, these prophages impact bacterial virulence in distinct ways: by secretion of phage-encoded toxins, modulation of the bacterial envelope, mediation of bacterial infectivity and the control of bacterial cell regulation. This review builds the argument that virulence-influencing prophages hold extensive, unexplored potential for biotechnology. More specifically, it highlights the development potential of novel therapies against infectious diseases, to address the current antibiotic resistance crisis. First, designer bacteriophages may serve to deliver genes encoding cargo proteins which repress bacterial virulence. Secondly, one may develop small molecules mimicking phage-derived proteins targeting central regulators of bacterial virulence. Thirdly, bacteria equipped with phage-derived synthetic circuits which modulate key virulence factors could serve as vaccine candidates to prevent bacterial infections. The development and exploitation of such antibacterial strategies will depend on the discovery of other prophage-derived, virulence control mechanisms and, more generally, on the dissection of the mutualistic relationship between temperate phages and bacteria, as well as on continuing developments in the synthetic biology field.

scholarly journals An Increased Risk of School-Aged Children with Viral Infection among Diarrhea Clusters in Taiwan during 2011–2019

Children ◽  
2021 ◽  
Vol 8 (9) ◽  
pp. 807
Author(s):  
Fu-Huang Lin ◽  
Yu-Ching Chou ◽  
Bao-Chung Chen ◽  
Jui-Cheng Lu ◽  
Chung-Jung Liu ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Infections ◽  
Bacterial Pathogens ◽  
Single Infection ◽  
Public Places ◽  
The Public ◽  
School Aged Children ◽  
Increased Risk ◽  
Epidemiological Characteristics

Acute diarrhea is mainly caused by norovirus and rotavirus. Numerous factors modify the risk of diarrhea cluster infections and outbreaks. The purpose of this study was to explore the epidemiological characteristics, differences, and trends in the distribution of viral and bacterial pathogens that cause diarrhea cluster events as well as the public places where diarrhea cluster events took place in Taiwan from 2011 to 2019. We examined publicly available, annual summary data on 2865 diarrhea clusters confirmed by the Taiwan Centers for Disease Control (CDC) from 2011 to 2019. There were statistically significant differences (p < 0.001) in event numbers of diarrhea clusters among viral and bacterial pathogens, and statistically significant differences (p < 0.001) in event numbers of diarrhea clusters among bacterial pathogens. There were also statistically significant differences (p < 0.001) in the event numbers of diarrhea clusters among public places. Norovirus infections were the first most numerous (77.1%, 1810/2347) diarrhea clusters among viral and bacterial infections. Among bacterial infections, Staphylococcus aureus infections accounted for the greatest number of diarrhea clusters (35.5%, 104/293). Schools were the places with the greatest number of diarrhea clusters (49.1%, 1406/2865) among various institutions. Norovirus single infection (odds ratio, OR = 4.423), Staphylococcus aureus single infection (OR = 2.238), and school (OR = 1.983) were identified as risk factors. This is the first report of confirmed events of diarrhea clusters taken from surveillance data compiled by Taiwan’s CDC (2011–2019). This study highlights the importance of long-term and geographically extended studies, particularly for highly fluctuating pathogens, to understand the implications of the transmission of diarrhea clusters in Taiwan’s populations. Importantly, big data have been identified that can inform future surveillance and research efforts in Taiwan.

scholarly journals Engineered Liposomes Protect Immortalized Immune Cells from Cytolysins Secreted by Group A and Group G Streptococci

Cells ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 166
Author(s):  
Hervé Besançon ◽  
Yu Larpin ◽  
Viktoria S. Babiychuk ◽  
René Köffel ◽  
Eduard B. Babiychuk
Keyword(s):  
Immune Cells ◽  
Bacterial Infections ◽  
Bacterial Pathogens ◽  
Host Cells ◽  
Human Pathogens ◽  
Efficient Treatment ◽  
Group G Streptococci ◽  
Cell Plasma ◽  
Successful Infection ◽  
Life Threatening

The increasing antibiotic resistance of bacterial pathogens fosters the development of alternative, non-antibiotic treatments. Antivirulence therapy, which is neither bacteriostatic nor bactericidal, acts by depriving bacterial pathogens of their virulence factors. To establish a successful infection, many bacterial pathogens secrete exotoxins/cytolysins that perforate the host cell plasma membrane. Recently developed liposomal nanotraps, mimicking the outer layer of the targeted cell membranes, serve as decoys for exotoxins, thus diverting them from attacking host cells. In this study, we develop a liposomal nanotrap formulation that is capable of protecting immortalized immune cells from the whole palette of cytolysins secreted by Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis—important human pathogens that can cause life-threatening bacteremia. We show that the mixture of cholesterol-containing liposomes with liposomes composed exclusively of phospholipids is protective against the combined action of all streptococcal exotoxins. Our findings pave the way for further development of liposomal antivirulence therapy in order to provide more efficient treatment of bacterial infections, including those caused by antibiotic resistant pathogens.

A Fused Thiophene-S,S-Dioxide-Based Super-Photostable Fluorescent Marker for Lipid Droplets

2020 ◽  
Author(s):  
Masayasu Taki ◽  
Keiji Kajiwara ◽  
Eriko Yamaguchi ◽  
Yoshikatsu Sato ◽  
Shigehiro Yamaguchi
Keyword(s):  
Small Molecules ◽  
Lipid Droplets ◽  
Trajectory Analysis ◽  
Super Resolution ◽  
Fluorescent Marker ◽  
Selective Staining ◽  
Fluorescent Markers ◽  
Biological Studies ◽  
Particle Level

Lipid droplets (LDs) are essential organelle in most eukaryotes, and tracking intracellular LDs dynamics using synthetic small molecules is crucial for biological studies. However, only a limited number of fluorescent markers that satisfy all requirements, such as the selective staining of LDs, high photostability, and sufficient biocompatibility, have been developed. Herein, we report a series of donor-p-acceptor dyes based on the thiophene-containing fused polycyclic scaffold [1]benzothieno[3,2-<i>b</i>][1]benzothiophene (BTBT), in which either or both thiophene rings are oxidized into thiophene-<i>S</i>,<i>S</i>-dioxide to form an electron-accepting building block. Among these dyes, LAQ1 satisfied all the aforementioned requirements, and allowed us capturing ultra-small LDs on the endoplasmic reticulum (ER) membrane by stimulation emission depletion (STED) microscopy with a super-resolution below the diffraction limit of light. Moreover, the extremely high photostability of LAQ1 enabled recording the lipolysis of LDs and the concomitant lipogenesis as well as long-term trajectory analysis of micro LDs at the single particle level in living cells.

scholarly journals Facile Use of ZnO Nanopowders to Protect Old Manual Paper Documents

Materials ◽  
2020 ◽  
Vol 13 (23) ◽  
pp. 5452
Author(s):  
Ludmila Motelica ◽  
Aurelian Popescu ◽  
Anca-Gabriela Răzvan ◽  
Ovidiu Oprea ◽  
Roxana-Doina Truşcă ◽  
...  
Keyword(s):  
Hand Hygiene ◽  
Antimicrobial Agents ◽  
Storage Conditions ◽  
Human Pathogens ◽  
Accessible Method

One of the main problems faced by libraries, archives and collectors is the mold degradation of the paper-based documents, books, artworks etc. Microfungi (molds) emerge in regular storage conditions of such items (humidity, usually over 50%, and temperatures under 21 °C). If the removal of the visible mycelium is relatively easy, there is always the problem of the subsequent appearance of mold as the spores remain trapped in the cellulosic, fibrillary texture, which acts as a net. Moreover, due to improper hand hygiene bacteria contamination, old books could represent a source of biohazard, being colonized with human pathogens. An easy and accessible method of decontamination, which could offer long term protection is therefore needed. Here, we present a facile use of the ZnO nanopowders as antimicrobial agents, suitable for cellulose-based products, conferring an extended antibacterial and anti-microfungal effect. The proposed method does not adversely impact on the quality of the cellulose documents and could be efficiently used for biodegradation protection.

Innovatory role of nanomaterials as bio-tools for treatment of cancer

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Khuram Shahzad Ahmad ◽  
Muntaha Talat ◽  
Shaan Bibi Jaffri ◽  
Neelofer Shaheen
Keyword(s):  
Cancer Treatment ◽  
Cancer Therapeutics ◽  
Physicochemical Characteristics ◽  
Global Scale ◽  
Current Review ◽  
Anti Cancer ◽  
Different Types ◽  
Cancerous Cells

AbstractConventional treatment modes like chemotherapy, thermal and radiations aimed at cancerous cells eradication are marked by destruction pointing the employment of nanomaterials as sustainable and auspicious materials for saving human lives. Cancer has been deemed as the second leading cause of death on a global scale. Nanomaterials employment in cancer treatment is based on the utilization of their inherent physicochemical characteristics in addition to their modification for using as nano-carriers and nano-vehicles eluted with anti-cancer drugs. Current work has reviewed the significant role of different types of nanomaterials in cancer therapeutics and diagnostics in a systematic way. Compilation of review has been done by analyzing voluminous investigations employing ERIC, MEDLINE, NHS Evidence and Web of Science databases. Search engines used were Google scholar, Jstore and PubMed. Current review is suggestive of the remarkable performance of nanomaterials making them candidates for cancer treatment for substitution of destructive treatment modes through investigation of their physicochemical characteristics, utilization outputs and long term impacts in patients.

scholarly journals 4,7-Disubstituted 7H-Pyrrolo[2,3-d]pyrimidines and Their Analogs as Antiviral Agents against Zika Virus

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3779
Author(s):  
Ruben Soto-Acosta ◽  
Eunkyung Jung ◽  
Li Qiu ◽  
Daniel J. Wilson ◽  
Robert J. Geraghty ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Dengue Virus ◽  
Small Molecules ◽  
Zika Virus ◽  
Antiviral Agents ◽  
Structural Features ◽  
Molecular Target ◽  
Core Structure ◽  
Human Pathogens ◽  
Important Group

Discovery of compound 1 as a Zika virus (ZIKV) inhibitor has prompted us to investigate its 7H-pyrrolo[2,3-d]pyrimidine scaffold, revealing structural features that elicit antiviral activity. Furthermore, we have demonstrated that 9H-purine or 1H-pyrazolo[3,4-d]pyrimidine can serve as an alternative core structure. Overall, we have identified 4,7-disubstituted 7H-pyrrolo[2,3-d]pyrimidines and their analogs including compounds 1, 8 and 11 as promising antiviral agents against flaviviruses ZIKV and dengue virus (DENV). While the molecular target of these compounds is yet to be elucidated, 4,7-disubstituted 7H-pyrrolo[2,3-d]pyrimidines and their analogs are new chemotypes in the design of small molecules against flaviviruses, an important group of human pathogens.

scholarly journals Label-Free Electrochemical Biosensor Based on Au@MoS₂–PANI for Escherichia coli Detection

Chemosensors ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 49
Author(s):  
Pushap Raj ◽  
Man Hwan Oh ◽  
Kyudong Han ◽  
Tae Yoon Lee
Keyword(s):  
Escherichia Coli ◽  
Bacterial Infections ◽  
Limit Of Detection ◽  
Bacterial Pathogens ◽  
Cost Effective ◽  
Covalent Immobilization ◽  
Label Free ◽  
Self Assembled Monolayer ◽  
Detection Range ◽  
Linear Detection

Bacterial infections have become a significant challenge in terms of public health, the food industry, and the environment. Therefore, it is necessary to address these challenges by developing a rapid, cost-effective, and easy-to-use biosensor for early diagnosis of bacterial pathogens. Herein, we developed a simple, label-free, and highly sensitive immunosensor based on electrochemical detection using the Au@MoS₂–PANI nanocomposite. The conductivity of the glassy carbon electrode is greatly enhanced using the Au@MoS₂–PANI nanocomposite and a self-assembled monolayer of mercaptopropionic acid on the gold nanoparticle surface was employed for the covalent immobilization of antibodies to minimize the nonspecific adsorption of bacterial pathogens on the electrode surface. The biosensor established a high selectivity and sensitivity with a low limit of detection of 10 CFU/mL, and detected Escherichia coli within 30 min. Moreover, the developed biosensor demonstrated a good linear detection range, practical utility in urine samples, and electrode regenerative studies.

scholarly journals Acute graft-versus-host disease: a bench-to-bedside update

Blood ◽  
2014 ◽  
Vol 124 (3) ◽  
pp. 363-373 ◽  
Author(s):  
Shernan G. Holtan ◽  
Marcelo Pasquini ◽  
Daniel J. Weisdorf
Keyword(s):  
Small Molecules ◽  
Graft Versus Host Disease ◽  
Host Disease ◽  
Multiple Modalities ◽  
Graft Versus Host ◽  
The Past ◽  
Prevention And Treatment ◽  
Near Future ◽  
Acute Graft

Abstract Over the past 5 years, many novel approaches to early diagnosis, prevention, and treatment of acute graft-versus-host disease (aGVHD) have been translated from the bench to the bedside. In this review, we highlight recent discoveries in the context of current aGVHD care. The most significant innovations that have already reached the clinic are prophylaxis strategies based upon a refinement of our understanding of key sensors, effectors, suppressors of the immune alloreactive response, and the resultant tissue damage from the aGVHD inflammatory cascade. In the near future, aGVHD prevention and treatment will likely involve multiple modalities, including small molecules regulating immunologic checkpoints, enhancement of suppressor cytokines and cellular subsets, modulation of the microbiota, graft manipulation, and other donor-based prophylaxis strategies. Despite long-term efforts, major challenges in treatment of established aGVHD still remain. Resolution of inflammation and facilitation of rapid immune reconstitution in those with only a limited response to corticosteroids is a research arena that remains rife with opportunity and urgent clinical need.

Antioestrogen inhibition of oestradiol-induced alterations in hypothalamic noradrenaline turnover

1985 ◽  
Vol 106 (1) ◽  
pp. 37-42 ◽  
Author(s):  
C. Hiemke ◽  
B. Poetz ◽  
R. Ghraf
Keyword(s):  
Brain Area ◽  
Serum Levels ◽  
Ovariectomized Rats ◽  
Noradrenaline Turnover ◽  
Stimulatory Action ◽  
Enhanced Sensitivity ◽  
Oestradiol Benzoate ◽  
Lh Release ◽  
Secretory System

ABSTRACT Long-term (4–6 weeks) ovariectomized rats were injected with either oestradiol benzoate (OB; 20 μg s.c.) or monohydroxytamoxifen (MTAM; 0·2 mg i.p.) plus OB. Oestradiol benzoate was administered at 12.00 h on day 0 and MTAM was given immediately before OB, followed by further injections twice daily to maintain sufficiently high antioestrogen levels. When given alone, OB reduced the serum levels of LH during the morning (08.00–09.00 h) and afternoon (17.30–18.30 h) hours of day 3 after priming. The feedback actions of OB on LH release were accompanied by time-dependent alterations of noradrenaline turnover in the preoptic–anterior hypothalamic brain area (POAH). On day 3 after priming the noradrenaline turnover rate was reduced in the morning and increased in the afternoon. The increase correlated with an enhanced sensitivity of the LH secretory system to progesterone. The antioestrogen MTAM blocked the OB-induced sensitization of LH release to the stimulatory action of progesterone and interfered with the stimulatory long-term effect of oestradiol on hypothalamic noradrenaline turnover. The data strongly support the view that the oestrogen-induced afternoon increase of noradrenaline turnover in the POAH represents a pre-requisite for the induction of LH surges. The stimulatory effect of oestradiol on hypothalamic noradrenaline turnover seems to be mediated by a classical oestrogen receptor mechanism. J. Endocr. (1985) 106, 37–42

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