Volume Articles

Benefits and Limitations of MALDI-TOF Mass Spectrometry for the Identification of Microorganisms

Jenna Rychert

ARUP Laboratories, Salt Lake City, Utah, USA

Matrix-assisted laser desorption-ionization time of flight mass spectrometry (MALDI-TOF MS) is replacing traditional methods for identifying microorganisms in the clinical laboratory. This relatively simple technique overcomes many of the challenges of identifying bacteria and fungi. As the technology has evolved, the expansion of the databases containing spectra of known organisms has allowed for the identification of species with similar phenotypic, genotypic, and biochemical properties that was not previously possible. This has resulted in improvements in clinical care including improving the diagnosis of infections caused by relatively rare species and decreasing the time to diagnosis. In many cases, this leads to a reduction in the time to appropriate therapy and even a decrease in the length of hospital stays. However, it is not without its limitations. Inherent similarities between organisms and a limited number of spectra in the database can lead to poor discrimination between species, as well as misidentifications. These errors occur with relatively low frequency and can typically be overcome with supplemental testing. The adoption of MALDI-TOF MS in the clinical microbiology laboratory is revolutionizing infectious disease diagnosis and clinical care.

Genetic Mutations Conferring Resistance to Candida albicans to Antifungal drugs: A Global Perspective and Regional Implications

PM Sawadogo^1,2, A Zida^1,2, I Sangaré^5,6, TK Guiguemdé^2,3, A. Sanfo¹, M. Idani¹, H Nacanabo¹, S Bamba^5,6, R Ouédraogo/Traoré^2,3, TR Guiguemdé^2,4

¹Parasitology-Mycology Department, Yalgado Ouedraogo University Hospital Center, Ouagadougou, Burkina Faso

²Training and Research Unit in Health Sciences, Ouaga University 1 Professor Joseph Ki-Zerbo (UO1 / PrZKZ), Ouagadougou, Burkina Faso

³Parasitology-Mycology Department, Charles de Gaulle University Hospital Center, sector 28 Ouagadougou, Burkina Faso

⁴Muraz Research Center, Bobo-Dioulasso, Burkina Faso

⁵Parasitology-Mycology Department, Souro Sanou University Hospital, Bobo Dioulasso, Burkina Faso

⁶Institut de Reccherche en Sciences de la Santé, Université Nazi Boni (UNB), Bobo Diuolasssa, Burkina Faso

This article aims to summarize the results of works from January 2013 to December 2017, on the molecular mechanisms of Candida albicans resistance to antifungal drugs. It is a prelude to a study on the molecular mechanisms of these resistances in Burkina Faso, with the aim of exploring new therapeutic solutions. Almost all studies have focused on the ERG11 gene as the most involved in azoles resistance. Mutations have also been demonstrated on other genes conferring resistance to other molecules such as CDR1 and 2, MRR1 and 2, TAC1 and ERG for polyenes, allylamines and azoles, FKS1 for echinocandins, FCA1 and FCY1 for pyrimidine analogues. Genetic mutations conferring the resistance of C. albicans to antifungals drugs worldwide are regularly reported, but in Burkina Faso we have no data on this subject. As a perspective therefore, a study on the molecular mechanisms of resistance of C. albicans to antifungals will be of great help in the fight against the resistance of this frequent yeast to antifungals drugs.

Mini Review on the Impact of Mobile Parts' Exchange During the DAIR Procedure (Debridement, Antibiotics, Irrigation, Retention) for Infected Total Joint Arthroplasties

Pascal Bezel¹, Sandro F. Fucentese², Jan Burkhard^1,3, Dominique Holy^1,3, Arend J. Nieuwland², Marco Burkhard², Ilker Uçkay^1,2,3,4*

¹Internal Medicine, Balgrist University Hospital, Zurich, Switzerland

²Department of Orthopedic Surgery, Balgrist University Hospital, Zurich, Switzerland

³Infectiology, Balgrist University Hospital, Zurich, Switzerland

⁴Unit for Clinical and Applied Research, Balgrist University Hospital, Zurich, Switzerland

A prosthetic joint infection (PJI) requires a combined approach (infectiology and surgery). The therapeutic DAIR approach (debridement, antibiotics, irrigation, and retention) is an option for acute and stable PJI yielding remission incidences that oscillate between 70% and 90%; in a literature mostly composed of retrospective single-center trials. DAIR can be performed with or without mobile part’s exchange during debridement. Scientific data proving the necessity of mobile part exchanges (by leaving other infected components in situ) remain scarce. In this narrative mini review, we evaluate the existing literature that analyses the benefit of exchanging mobile parts with at least ten own cases. We moreover discuss the optimal duration of concomitant targeted systemic antibiotic therapy and reveal some insights in the surgical difficulties in performing DAIR. Our conclusion tends to favor of the mobile part’s exchange whenever feasible.

Clinical Approaches of HIV-1/HTLV-1 Co-infection Still Keep their Mysteries

Gerges Rizkallah¹, Renaud Mahieux², Hélène Dutartre²

¹Faculty of Public Health, Sagesse University, Beirut, Lebanon

²Équipe oncogenèse rétrovirale, équipe labellisée «FRM», CIRI – Centre International de Recherche en Infectiologie, Univ Lyon, Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR, ENS Lyon, Lyon, France

Two retroviruses emerged in the 1980s : HTLV-1 and HIV-1^1,2,3. HTLV-1 infects 5-10 million people worldwide and is detected in highly endemic areas, such as Japan, sub-Saharan Africa, the Caribbean region, South America⁴ as well as in Australian indigenous⁵. According to the UNAIDS’s 2018 fact sheet, HIV-1 is endemic worldwide, infects 37.9 million people and is particularly prevalent in central and South Africa, the Caribbean region, Latin America, South-East Asia and Eastern Europe⁶. HTLV-1 or HIV-1 infected individuals develop chronic infections. Only in 1-10% of infected carriers, HTLV-1 leads either to the development of Adult T-cell Leukemia/Lymphoma (ATLL), or of Tropical Spastic Paraparesis/HTLV-1 Associated Myelopathy (TSP/HAM)⁷. In most chronically infected people, HIV-1 infection leads to an Acquired Immunodeficiency Syndrome (AIDS), and around 22% of the death causes among HIV-infected patients remains AIDS-related⁶. The aim of this mini-review is to highlight some of the points discussed in the review ‘’HTLV-1, the Other Pathogenic Yet Neglected Human Retrovirus: From Transmission to Therapeutic Treatment’’⁸. First, it will focus on the similarities regarding transmission mechanisms and cellular tropism between these retroviruses. Then, starting from the therapeutic protocols currently used in the treatment of each of these retroviral infections, this mini-review will summarize the therapeutic protocols used for co-infections management.

Rifamycin SV Anti-inflammatory and Immunomodulatory Activities for Treatment of Mucosal and Liver Inflammation

Caridad Rosette, Alessandro Mazzetti, Roberto Camerini, Luigi Moro, Mara Gerloni*

Cosmo Pharmaceuticals, Riverside II. Sir John Rogerson’s Quay, Dublin, Ireland

Rifamycin SV (rifamycin), is a member of the ansamycin family of antimicrobial compounds which kills bacteria commonly associated with infectious diarrhea and other enteric infections. For colonic diseases like diverticulitis, inflammatory bowel syndrome (IBS) or inflammatory bowel disease (IBD), bacterial proliferation or microbial dysbiosis is associated with a strong inflammatory component. This inflammation has a profound influence on the liver via the gut-liver axis. This review summarizes the anti-inflammatory activities of rifamycin based on analyses of its impact on two key regulators of inflammation: PXR and NFκB. Rifamycin was found to activate PXR and two of its downstream targets, CYP3A4 and PgP, in liver and intestinal cell lines. Rifamycin also directly inhibited NFκB in a cell line which lacks PXR expression. These dual activities likely explain the inhibition of pro-inflammatory cytokine secretion from human colonic cells lines and activated CD4⁺ T cells. These experimental data define the immune regulatory characteristics of rifamycin and an emerging role in the treatment of both gastrointestinal (GI) and liver disorders.

Invasion of Human Nails by Microsporum canis

Daiane Flores Dalla Lana¹*, Paula Reginatto², William Lopes³, Marilene Henning Vainstein³, Alexandre Meneghello Fuentefria^1,2

¹Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Brazil

²Programa de Pós-graduação em Microbiologia Agrícola e do Ambiente, Universidade Federal do Rio Grande do Sul, Brazil

³Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Brazil

We report the invasion of the human nail plate by the dermatophytic species Microsporum canis, which was recently described as a biofilm former, in Scanning Electron Microscopy (SEM) images. With the images it was possible to evidence the propagation and aggregation of hyphae on the nails and also the formation of biofilm, as a pathogenicity and virulence factor of the species in cases of onychomycosis.

With a Little Help from Good Friends – Boosters for the Prevention of Undesired Enzymatic Degradation of Anti-infective Drugs

Franz Bracher*

Ludwig-Maximilians University, Department of Pharmacy - Center for Drug Research, Butenandtstr., Munich, Germany

The development of anti-infective drugs has been one of the most impressive progresses in drug therapy in the past century. However, some of the promising antibacterial and antiviral drugs lost activity after being used in therapy for some time. Typically, this is due to the development of resistance phenomena, among which the expression of drug-degrading enzymes is one major aspect. In other cases, enzymatic degradation of anti-infective drugs by mammalian enzymes in the liver (or kidney) can limit the efficacy of the drugs. In all of these cases, selection of a drug from a different class is a therapeutic opportunity. Alternatively, the original drug can be used further in combination with other compounds named boosters, pharmacokinetic enhancers or antibiotic adjuvants. These compounds are used in combination with the primary anti-infective agent, but not for their direct effects on the infection itself, but since they enhance or restore the activity of the drug. This mini-review gives an overview on the therapeutically most important classes of boosters/antibiotic enhancers, like β-lactamase inhibitors, inhibitors of CYP enzymes in HIV therapy and hepatitis C. Inhibitors of efflux pumps in pathogenic bacteria and fungi will be addressed shortly.

Multidrug Resistant Probiotics as an Alternative to Antibiotic Probiotic therapy

Dhanashree Lokesh¹, Kammara Rajagopal^1,2, Jae Ho Shin²*

¹Department of Protein Chemistry and Technology, CSIR-CFTRI, Mysore, India

²School of Applied Biosciences, Kyungpook National University, Daegu, Korea

Drug-resistance is a major problem globally, the number of drug-resistant bacteria has increased substantially through horizontal gene transfer. Even Mycobacterium tuberculosis are reported to have acquired antitubercular drug-resistance and named as MDR Mtb. The acquisition of immunity has not given up, here; it is needed to be a continuous procedure. Further causing the microbial adapting to a very high and larger number of drugs recognized as extreme drug and total drug-resistance. The mechanistic aspects of MDR Mtb are well understood. Nevertheless, this is not the case with Probiotic microbes such as Bifidobacterium adolescentis. Herein, we report the mechanistic aspects of antitubercular drug-resistance in this organism for the first time. This review discusses the report by a mutation that confers multi drug-resistance in Bifidobacteria.

Commentary: Differential Humoral and Cellular Immunity Induced by Vaccination using Plasmid DNA and Protein Recombinant Expressing the NS3 Protein of Dengue Virus type 3

Angel Ramos-Ligonio¹, Aracely López-Monteon¹*

¹LADISER Inmunología y Biología Molecular, Universidad Veracruzana, Orizaba, Veracruz, México