scholarly journals Antimicrobial activity of Mycobacteriophage D29 Lysin B during Mycobacterium ulcerans infection

2018 ◽  
Author(s):  
Alexandra G. Fraga ◽  
Gabriela Trigo ◽  
Juan Dominguez ◽  
Rita Silva-Gomes ◽  
Carine M. Gonçalves ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Soft Tissues ◽  
Buruli Ulcer ◽  
Mycobacterium Ulcerans ◽  
World Health ◽  
Lipolytic Enzyme ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Advanced Stages ◽  
Health Organization

Buruli Ulcer (BU) is a cutaneous disease caused by Mycobacterium ulcerans. The pathogenesis of BU is closely related to the secretion of the toxin mycolactone that induces extensive destruction of the skin and soft tissues. Although the World Health Organization recommends a combination of rifampicin and streptomycin for the treatment of BU, clinical management of advanced stages often requires extensive surgical resection of the infected tissue. Therefore, it is important to develop alternative strategies for the treatment of BU. Endolysins (lysins) are phage encoded enzymes that degrade peptidoglycan of bacterial cell walls. Over the past years, lysins have been emerging as alternative antimicrobial agents against Gram-positive bacteria. Amongst Gram-positive bacteria, mycobacteria have an unusual outer membrane that is covalently attached to the mycolyl arabinogalactan-peptidoglycan complex. To overcome this additional barrier to phage-mediated lysis, some mycobacteriophages encode a lipolytic enzyme, Lysin B (Lys B). In this study, we demonstrated for the first time that recombinant Lys B displays lytic activity against M. ulcerans isolates. Moreover, using a mouse model of M. ulcerans footpad infection, we show that subcutaneous treatment with Lys B leads to a reduction in bacterial burdens, associated with IFN-γ and TNF production in the draining lymph node. These findings highlight the potential use of lysins as a novel therapeutic approach against this neglected tropical disease.

scholarly journals Buruli Ulcer: Review of a Neglected Skin Mycobacterial Disease

2017 ◽  
Vol 56 (4) ◽  
Author(s):  
Jeannette Guarner
Keyword(s):  
Clinical Presentation ◽  
Oral Treatment ◽  
Buruli Ulcer ◽  
Mycobacterium Ulcerans ◽  
World Health ◽  
Tissue Necrosis ◽  
Content Type ◽  
Skin Nodule ◽  
The World ◽  
Health Organization

ABSTRACTBuruli ulcer is caused byMycobacterium ulcerans. This neglected disease occurs in scattered foci around the world, with a higher concentration of cases in West Africa. The mycobacteria produce mycolactones that cause tissue necrosis. The disease presents as a painless skin nodule that ulcerates as necrosis expands. Finding acid-fast bacilli in smears or histopathology, culturing the mycobacteria, and performingM. ulceransPCR in presumptive cases confirm the diagnosis. Medical treatment with oral rifampin and intramuscular streptomycin or oral treatment with rifampin plus clarithromycin for 8 weeks is supported by the World Health Organization. This review summarizes the epidemiology, pathogenesis, clinical presentation, diagnostic tests, and advances in treatment.

scholarly journals Skin-specific antibodies neutralizing mycolactone toxin during the spontaneous healing of Mycobacterium ulcerans infection

2020 ◽  
Vol 6 (9) ◽  
pp. eaax7781 ◽  
Author(s):  
Mélanie Foulon ◽  
Amélie Pouchin ◽  
Jérémy Manry ◽  
Fida Khater ◽  
Marie Robbe-Saule ◽  
...  
Keyword(s):  
Healing Process ◽  
Buruli Ulcer ◽  
Mycobacterium Ulcerans ◽  
World Health ◽  
Immunomodulatory Activity ◽  
Spontaneous Healing ◽  
Specific Antibodies ◽  
Skin Ulcers ◽  
Chronic Skin ◽  
Health Organization

Buruli ulcer, a neglected tropical infectious disease, is caused by Mycobacterium ulcerans. Without treatment, its lesions can progress to chronic skin ulcers, but spontaneous healing is observed in 5% of cases, suggesting the possible establishment of a host strategy counteracting the effects of M. ulcerans. We reveal here a skin-specific local humoral signature of the spontaneous healing process, associated with a rise in antibody-producing cells and specific recognition of mycolactone by the mouse IgG2a immunoglobulin subclass. We demonstrate the production of skin-specific antibodies neutralizing the immunomodulatory activity of the mycolactone toxin, and confirm the role of human host machinery in triggering effective local immune responses by the detection of anti-mycolactone antibodies in patients with Buruli ulcer. Our findings pave the way for substantial advances in both the diagnosis and treatment of Buruli ulcer in accordance with the most recent challenges issued by the World Health Organization.

scholarly journals Bactericidal Activity of Rifampin-Amikacin against Mycobacterium ulcerans in Mice

2002 ◽  
Vol 46 (10) ◽  
pp. 3193-3196 ◽  
Author(s):  
Herve Dega ◽  
Abdelhalim Bentoucha ◽  
Jerome Robert ◽  
Vincent Jarlier ◽  
Jacques Grosset
Keyword(s):  
Clinical Trial ◽  
Bactericidal Activity ◽  
Buruli Ulcer ◽  
Acid Fast Bacillus ◽  
Drug Dosage ◽  
Mycobacterium Ulcerans ◽  
World Health ◽  
Health Organization ◽  
The Impact ◽  
Lesion Index

ABSTRACT To identify the most active curative treatment of Buruli ulcer, two regimens incorporating the use of rifampin (RIF) were compared with the use of RIF alone in a mouse footpad model of Mycobacterium ulcerans infection. Treatments began after footpad swelling from infection and continued for 12 weeks with five doses weekly of one of the following regimens: (i) 10 mg of RIF/kg alone; (ii) 10 mg of RIF/kg and 100 mg of amikacin (AMK)/kg; and (iii) 10 mg of RIF/kg, 100 mg of clarithromycin (CLR)/kg, and 50 mg of sparfloxacin (SPX)/kg. The activity of each regimen was assessed in terms of the reduction of the average lesion index and acid-fast bacillus (AFB) and CFU counts. All three regimens displayed various degrees of bactericidal activity against M. ulcerans. The ranking of bactericidal activity was found to be as follows: RIF-AMK > RIF-CLR-SPX > RIF. RIF-AMK was able to cure M. ulcerans-infected mice and prevent relapse 26 weeks after completion of treatment. To determine the impact of different rhythms of administration of RIF-AMK on the suppression of M.ulcerans growth, mice were given the RIF-AMK combination for 4 weeks but doses were administered either 5 days a week or twice or once weekly. After completion of treatment, the mice were kept under supervision for 30 additional weeks. M. ulcerans was considered to have grown in the footpad if swelling was visually observed and harvests contained more than 5 × 105 AFB per footpad. The proportion of mice in which growth of M. ulcerans occurred, irrespective of drug dosage, was compared with the control mice to determine the proportion of M. ulcerans killed. Each dosage of RIF-AMK was bactericidal for M. ulcerans (P < 0.001), but the effect was significantly stronger in mice treated 5 days per week. The promising results of RIF-AMK treatment in M. ulcerans-infected mice support the clinical trial that is currently in progress under World Health Organization auspices in Ghana.

Susceptibility of Gram-positive bacteria from ICU patients in UK hospitals to antimicrobial agents

2003 ◽  
Vol 54 (3) ◽  
pp. 179-187 ◽  
Author(s):  
A.P Johnson ◽  
C Henwood ◽  
S Mushtaq ◽  
D James ◽  
M Warner ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Gram Positive ◽  
Icu Patients ◽  
Gram Positive Bacteria

scholarly journals Antimicrobial Nodule-Specific Cysteine-Rich Peptides Induce Membrane Depolarization-Associated Changes in the Transcriptome of Sinorhizobium meliloti

2013 ◽  
Vol 79 (21) ◽  
pp. 6737-6746 ◽  
Author(s):  
Hilda Tiricz ◽  
Attila Szűcs ◽  
Attila Farkas ◽  
Bernadett Pap ◽  
Rui M. Lima ◽  
...  
Keyword(s):  
Stress Responses ◽  
Sinorhizobium Meliloti ◽  
Antimicrobial Agents ◽  
Cellular Functions ◽  
Gram Positive ◽  
Content Type ◽  
Gram Positive Bacteria ◽  
Peptide Family ◽  
Wide Range ◽  
Natural Target

ABSTRACTLeguminous plants establish symbiosis with nitrogen-fixing alpha- and betaproteobacteria, collectively called rhizobia, which provide combined nitrogen to support plant growth. Members of the inverted repeat-lacking clade of legumes impose terminal differentiation on their endosymbiotic bacterium partners with the help of the nodule-specific cysteine-rich (NCR) peptide family composed of close to 600 members. Among the few tested NCR peptides, cationic ones had antirhizobial activity measured by reduction or elimination of the CFU and uptake of the membrane-impermeable dye propidium iodide. Here, the antimicrobial spectrum of two of these peptides, NCR247 and NCR335, was investigated, and their effect on the transcriptome of the natural targetSinorhizobium melilotiwas characterized. Both peptides were able to kill quickly a wide range of Gram-negative and Gram-positive bacteria; however, their spectra were only partially overlapping, and differences were found also in their efficacy on given strains, indicating that the actions of NCR247 and NCR335 might be similar though not identical. Treatment ofS. meliloticultures with either peptide resulted in a quick downregulation of genes involved in basic cellular functions, such as transcription-translation and energy production, as well as upregulation of genes involved in stress and oxidative stress responses and membrane transport. Similar changes provoked mainly in Gram-positive bacteria by antimicrobial agents were coupled with the destruction of membrane potential, indicating that it might also be a common step in the bactericidal actions of NCR247 and NCR335.

Emerging Resistance to Antimicrobial Agents in Gram-Positive Bacteria

Drugs ◽  
1996 ◽  
Vol 51 (Supplement 1) ◽  
pp. 6-12 ◽  
Author(s):  
Martin G. Cormican ◽  
Ronald N. Jones
Keyword(s):  
Antimicrobial Agents ◽  
Gram Positive ◽  
Gram Positive Bacteria

scholarly journals Construction of Leaderless-Bacteriocin-Producing Bacteriophage Targeting E. coli and Neighboring Gram-Positive Pathogens

2021 ◽  
Author(s):  
Yoshimitsu Masuda ◽  
Shun Kawabata ◽  
Tatsuya Uedoi ◽  
Ken-ichi Honjoh ◽  
Takahisa Miyamoto
Keyword(s):  
Antimicrobial Agents ◽  
Host Strain ◽  
Phage Resistance ◽  
Gram Positive ◽  
Gram Negative ◽  
E Coli ◽  
Gram Positive Bacteria ◽  
T7 Phage

We demonstrated that we could combine LLB and phage to construct promising novel antimicrobial agents, LLB-phage. The first LLB-phage, lnqQ -T7 phage, can control the growth of both the Gram-negative host strain and neighboring Gram-positive bacteria while preventing the emergence of phage resistance in the host strain.

scholarly journals Advances in the Treatment of Yaws

2018 ◽  
Vol 3 (3) ◽  
pp. 92 ◽  
Author(s):  
Michael Marks
Keyword(s):  
Soft Tissues ◽  
Central Africa ◽  
Standard Of Care ◽  
World Health ◽  
South East Asia ◽  
The Pacific ◽  
West And Central Africa ◽  
Resistance To Penicillin ◽  
Health Organization ◽  
Oral Azithromycin

Yaws is one of the three endemic treponematoses and is recognised by the World Health Organization as a neglected tropical disease. Yaws is currently reported in 15 countries in the Pacific, South-East Asia, West and Central Africa, predominantly affects children, and results in destructive lesions of the skin and soft tissues. For most of the twentieth century penicillin-based treatment was the standard of care and resistance to penicillin has still not been described. Recently, oral azithromycin has been shown to be an effective treatment for yaws, facilitating renewed yaws eradication efforts. Resistance to azithromycin is an emerging threat and close surveillance will be required as yaws eradication efforts are scaled up globally.

Pharmaco-EcoMicrobiology and Its Potential Role in Medical and Environmental Sciences

2012 ◽  
pp. 291-302
Author(s):  
Mohd. Shahid ◽  
Hridesh Mishra ◽  
Hemant Kumar Mishra ◽  
Trivendra Tripathi ◽  
Haris M. Khan ◽  
...  
Keyword(s):  
Information Technologies ◽  
Antimicrobial Agents ◽  
Drug Effects ◽  
Pharmacy Education ◽  
World Health ◽  
Adverse Drug Effects ◽  
Pharmaceutical Industries ◽  
Health Organization

Despite the call of the World Health Organization (WHO) for “Pharmacovigilance,” i.e. the monitoring, detection, assessment, and prevention of any adverse reactions, poor attention has been given to identify the long term and short term Adverse Effects (ADEs) of antimicrobial agents on the environment. It is obvious that most of the health sectors across the globe are occupied by infectious diseases (e.g. tuberculosis, HIV, and hepatitis), and to combat such threats, the pharmaceutical industries are pouring tons of drugs and reagents into a market worth billions of dollars. The discharge of these products into the ecosystem is potentially a threat to the environment and human health. In this chapter, the authors depicted a recently described terminology, “Pharmaco-EcoMicrobiology” (PEcM), that could cover these problems and their possible solutions on medical and environmental aspects. In this regard, the role of pharmacoinformatics could also be crucial, since it can provide swift information for implementation and use of information technologies for the discovery and development of drugs as well as in pharmacy education and also the detection and combat of adverse drug effects.

Disease Changes: Microbial and Vector Adaptation

2009 ◽  
Author(s):  
A. D. Cliff ◽  
M.R. Smallman-Raynor ◽  
P. Haggett ◽  
D.F. Stroup ◽  
S.B. Thacker
Keyword(s):  
Influenza A ◽  
Antimicrobial Agents ◽  
Pathogen Resistance ◽  
World Health ◽  
Ecological Change ◽  
Human Pathogens ◽  
Continuous State ◽  
Challenges And Opportunities ◽  
Health Organization ◽  
Microbial Change

In this and the next four chapters, we examine five change agents which have facilitated the emergence and re-emergence of infectious human diseases. Each agent—microbial and genetic adaptation, technology and industry, changes in host populations, environmental and ecological change, and war as a disease amplifier—has underpinned over the centuries both the appearance of new diseases and the waxing and waning of familiar infections. As shown in Figure II.1, the agents are not independent and commonly interact in complex ways to facilitate microbe emergence and re-emergence at different times and in different geographical locations. Accordingly, we also explore these interactions in our account. We begin here with microbial and vector adaptation. Disease microbes are in a continuous state of evolution, responding and adapting to the challenges and opportunities afforded by their hosts and their environments (Morse 1995). New pathogens are evolving, old pathogens are developing enhanced virulence and new clinical expressions, and susceptible pathogens are acquiring resistance to antimicrobial agents. In parallel, the environmental tolerance bands of both old and new pathogens are also changing (Cohen 1998). Not only are disease microbes in a continuous state of evolution. So, too, are the arthropod vectors that transmit many human pathogens. In the second half of the twentieth century, many of these vectors have developed tolerance to an expanding range of insecticides, larvicides, pupicides, and other chemical agents used in their control (World Health Organization 1992c). Against this background, our examination of microbial change and vector adaptation is structured around the three interlinked themes shown in Figure 4.1. We begin in Section 4.2 by examining the issue of natural variation in pathogens and illustrate this with special reference to the emergence and spread of novel subtypes of influenza A virus. We then examine the topic of selective pressure and genetic change in the context of the man-made problems of pathogen resistance to antimicrobials (Section 4.3) and vector resistance to insecticides (Section 4.4). The processes of microbial change and vector adaptation are not intrinsically geographical but they take place within, and are inextricably linked to, specific geographical environments. This gives a strong geographical emphasis to our discussion.

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