C-Phycocyanin Prevents Oxidative Stress, Inflammation, and Lung Remodeling in an Ovalbumin-Induced Rat Asthma Model.

Asthma is a chronic immunological disease related to oxidative stress and chronic inflammation; both processes promote airway remodeling with collagen deposition and matrix thickening, causing pulmonary damage and lost function. This study investigates the immunomodulation of C-phycocyanin (CPC), a natural blue pigment purified from cyanobacteria, as a potential alternative treatment to prevent the remodeling process against asthma. We conducted experiments using ovalbumin (OVA) to induce asthma in Sprague Dawley rats. Animals were divided into five groups: (1) sham + vehicle, (2) sham + CPC, (3) asthma + vehicle, (4) asthma + CPC, and (5) asthma + methylprednisolone (MP). Our findings reveal that asthma promotes hypoxemia, leukocytosis, and pulmonary myeloperoxidase (MPO) activity by increasing lipid peroxidation, reactive oxygen and nitrogen species, inflammation associated with Th2 response, and airway remodeling in the lungs. CPC and MP treatment partially prevented these physiological processes with similar action on the biomarkers evaluated. In conclusion, CPC treatment enhanced the antioxidant defense system, thereby preventing oxidative stress and reducing airway inflammation by regulating pro-inflammatory and anti-inflammatory cytokines, consequently avoiding asthma-induced airway remodeling.

Anti-Mycobacterium tuberculosis Activity of Esters of Quinoxaline 1,4-Di-N-Oxide.

Tuberculosis continues to be a public health problem in the world, and drug resistance has been a major obstacle in its treatment. Quinoxaline 1,4-di-N-oxide has been proposed as a scaffold to design new drugs to combat this disease. To examine the efficacy of this compound, this study evaluates methyl, ethyl, isopropyl, and n-propyl esters of quinoxaline 1,4-di-N-oxide derivatives in vitro against Mycobacterium tuberculosis (pansusceptible and monoresistant strains). Additionally, the inhibitory effect of esters of quinoxaline 1,4-di-N-oxide on M. tuberculosis gyrase supercoiling was examined, and a stability analysis by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS) was also carried out. Results showed that eight compounds (T-007, T-018, T-011, T-069, T-070, T-072, T-085 and T-088) had an activity similar to that of the reference drug isoniazid (minimum inhibitory concentration (MIC) = 0.12 µg/mL) with an effect on nonreplicative cells and drug monoresistant strains. Structural activity relationship analysis showed that the steric effect of an ester group at 7-position is key to enhancing its biological effects. Additionally, T-069 showed a high stability after 24 h in human plasma at 37 °C.

Aetiology and Significance of Hospital-Acquired Infections in Mexico.

Hospital-acquired infections (HAIs) are infections that develop in the hospital environment and can be acquired by a patient or hospital staff. They are complications that combine diverse risk factors that make an individual susceptible and are frequently caused by endogenous and exogenous bacterial agents. The most commonly studied etiological agents are bacteria and fungi, with the former representing the most common etiological agents reported to the Hospital Epidemiological Surveillance Network (RHOVE) between 2007 and 2012. Among these agents were Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, coagulase-negative Staphylococci (CNS), Enterococcus spp., and Streptococcus pneumoniae. Although obligate anaerobic bacteria are also etiological agents of HAIs, clinical laboratories do not usually perform bacteriological tests to isolate and identify these bacteria. As a result, patients are at a greater risk of not surviving an infection and the epidemiology of this bacterial group is unknown. An important problem associated with HAIs is bacterial multiple drug resistance, which not only increases morbidity and mortality but also the cost of inpatient care. The aim of this review is to provide current information to healthcare professionals on the status of HAIs in Mexico with an emphasis on the etiology, diagnosis, and antimicrobial resistance.

Expression of Antimicrobial Peptides in Human Monocytic Cells and Neutrophils in Response to Dengue Virus Type 2.

BACKGROUND/AIMS: The innate immune response is remarkably important for controlling infections. Information about the participation of antimicrobial peptides (AMPs) in response to dengue virus (DENV) is scarce. The aim of this study was to examine the AMP response to DENV-2 in human THP-1 cells and neutrophils. METHODS: Protein and mRNA levels of two AMPs - hBD-1 and cathelicidin LL-37 - were assessed in DENV-infected macrophage-like THP-1 cells using qRT-PCR and indirect immunofluorescence. Also, mRNA levels of α-defensins (hDEFAs) and LL-37 were examined by qRT-PCR in human neutrophils taken from peripheral blood and treated with DENV-2. RESULTS: mRNA expression of hBD-1 rose in THP-1 cells at 24-72 h, while protein expression increased later, from 48 to 72 h after infection. Cathelicidin LL-37 mRNA expression of DENV-infected THP-1 cells was observed at 6-48 h after infection, while protein levels increased importantly up to 72 h after infection. Regarding neutrophils, the mRNA expression of hDEFAs and LL-37 increased slightly at 2 and 5 h after the contact with DENV-2. CONCLUSION: THP-1 cells and human neutrophils strongly respond to DENV by producing AMPs: hBD-1 and LL-37 for the THP-1 cells and hDEFAs and LL-37 for neutrophils. However, the direct effect of these molecules on DENV particles remains unclear.

Influence of levamisole and Freund's adjuvant on mouse immunisation with antigens of adults of the liver fluke Fasciola hepatica Linnaeus, 1758.

We have studied the influence of both levamisole (AL) and Freund's adjuvant (AF) on the immunisation of mice with the secretory antigens of adults of the liver fluke Fasciola hepatica Linnaeus, 1758. Total IgG antibodies were detected in all groups where the F. hepatica antigen was administered, been levels of IgG1 increased respect to IgG2a antibodies. During immunisation, IL-4 and IFN-γ were only detected in AL and AF groups, but after infection, IL-4 boosted in all groups. IFN-γ increased two fold in AF and AL groups compared to the saline solution (AS) group. Worm recovering was of 32-35% in groups administered without antigen whereas in AS, AL and AF groups recovering was of 25%, 12% and 8%, respectively. Macroscopical lesions in the liver were scarce in AL and AF groups. Our data suggest that immunisation of mice with antigens of F. hepatica enhances the immune response avoiding both liver damage and worm establishment after challenge infection. The murine model of fasciolosis has appeared to be useful to elucidate the mechanism by which the parasite modulates immune responses toward a Th2 type but also the development of Th1 type-inducing vaccines.

Macrophage Activation by Ursolic and Oleanolic Acids during Mycobacterial Infection.

Oleanolic (OA) and ursolic acids (UA) are triterpenes that are abundant in vegetables, fruits and medicinal plants. They have been described as active moieties in medicinal plants used for the treatment of tuberculosis. In this study, we analyzed the effects of these triterpenes on macrophages infected in vitro with Mycobacterium tuberculosis (MTB). We evaluated production of nitric oxide (NO), reactive oxygen species (ROS), and cytokines (TNF-α and TGF-ß) as well as expression of cell membrane receptors (TGR5 and CD36) in MTB-infected macrophages following treatment with OA and UA. Triterpenes caused reduced MTB growth in macrophages, stimulated production of NO and ROS in the early phase, stimulated TNF-α, suppressed TGF-ß and caused over-expression of CD36 and TGR5 receptors. Thus, our data suggest immunomodulatory properties of OA and UA on MTB infected macrophages. In conclusion, antimycobacterial effects induced by these triterpenes may be attributable to the conversion of macrophages from stage M2 (alternatively activated) to M1 (classically activated).

Mycobacteria entry and trafficking into endothelial cells.

Endothelial cells are susceptible to infection by mycobacteria, but the endocytic mechanisms that mycobacteria exploit to enter host cells and their mechanisms of intracellular transport are completely unknown. Using pharmacological inhibitors, we determined that the internalization of Mycobacterium tuberculosis (MTB), Mycobacterium smegmatis (MSM), and Mycobacterium abscessus (MAB) is dependent on the cytoskeleton and is differentially inhibited by cytochalasin D, nocodazole, cycloheximide, wortmannin, and amiloride. Using confocal microscopy, we investigated their endosomal trafficking by analyzing Rab5, Rab7, LAMP-1, and cathepsin D. Our results suggest that MSM exploits macropinocytosis to enter endothelial cells and that the vacuoles containing these bacteria fuse with lysosomes. Conversely, the entry of MTB seems to depend on more than one endocytic route, and the observation that only a subset of the intracellular bacilli was associated with phagolysosomes suggests that these bacteria are able to inhibit endosomal maturation to persist intracellularly. The route of entry for MAB depends mainly on microtubules, which suggests that MAB uses a different trafficking pathway. However, MAB is also able to inhibit endosomal maturation and can replicate intracellularly. Together, these findings provide the first evidence that mycobacteria modulate proteins of host endothelial cells to enter and persist within these cells.

A population-based study of first and second-line drug-resistant tuberculosis in a high-burden area of the Mexico/United States border.

The resistance of 139 Mycobacterium tuberculosis (MTB) isolates from the city of Monterrey, Northeast Mexico, to first and second-line anti-TB drugs was analysed. A total of 73 isolates were susceptible and 66 were resistant to anti-TB drugs. Monoresistance to streptomycin, isoniazid (INH) and ethambutol was observed in 29 cases. Resistance to INH was found in 52 cases and in 29 cases INH resistance was combined with resistance to two or three drugs. A total of 24 isolates were multidrug-resistant (MDR) resistant to at least INH and rifampicin and 11 MDR cases were resistant to five drugs. The proportion of MDR-TB among new TB cases in our target population was 0.72% (1/139 cases). The proportion of MDR-TB among previously treated cases was 25.18% (35/139 cases). The 13 polyresistant and 24 MDR isolates were assayed against the following seven second-line drugs: amikacin (AMK), kanamycin (KAN), capreomycin (CAP), clofazimine (CLF), ethionamide (ETH), ofloxacin (OFL) and cycloserine (CLS). Resistance to CLF, OFL or CLS was not observed. Resistance was detected to ETH (10.80%) and to AMK (2.70%), KAN (2.70%) and CAP (2.70%). One isolate of MDR with primary resistance was also resistant to three second-line drugs. Monterrey has a high prevalence of MDR-TB among previously treated cases and extensively drug-resistant-MTB strains may soon appear.

Antiprotozoal and antimycobacterial activities of Persea americana seeds.

BACKGROUND: Persea americana seeds are widely used in traditional Mexican medicine to treat rheumatism, asthma, infectious processes as well as diarrhea and dysentery caused by intestinal parasites. METHODS: The chloroformic and ethanolic extracts of P. americana seeds were prepared by maceration and their amoebicidal, giardicidal and trichomonicidal activity was evaluated. These extracts were also tested against Mycobacterium tuberculosis H37Rv, four mono-resistant and two multidrug resistant strains of M. tuberculosis as well as five non tuberculosis mycobacterium strains by MABA assay. RESULTS: The chloroformic and ethanolic extracts of P. americana seeds showed significant activity against E. histolytica, G. lamblia and T. vaginalis (IC50 <0.634 µg/ml). The chloroformic extract inhibited the growth of M. tuberculosis H37Rv, M. tuberculosis MDR SIN 4 isolate, three M. tuberculosis H37Rv mono-resistant reference strains and four non tuberculosis mycobacteria (M. fortuitum, M. avium, M. smegmatis and M. absessus) showing MIC values ≤50 µg/ml. Contrariwise, the ethanolic extract affected only the growth of two mono-resistant strains of M. tuberculosis H37Rv and M. smegmatis (MIC ≤50 µg/ml). CONCLUSIONS: The CHCl3 and EtOH seed extracts from P. americana showed amoebicidal and giardicidal activity. Importantly, the CHCl3 extract inhibited the growth of a MDR M. tuberculosis isolate and three out of four mono-resistant reference strains of M. tuberculosis H37Rv, showing a MIC = 50 µg/ml. This extract was also active against the NTM strains, M. fortuitum, M. avium, M. smegmatis and M. abscessus, with MIC values <50 µg/ml.

Ursolic and oleanolic acids as antimicrobial and immunomodulatory compounds for tuberculosis treatment.

BACKGROUND: New alternatives for the treatment of Tuberculosis (TB) are urgently needed and medicinal plants represent a potential option. Chamaedora tepejilote and Lantana hispida are medicinal plants from Mexico and their hexanic extracts have shown antimycobacterial activity. Bioguided investigation of these extracts showed that the active compounds were ursolic acid (UA) and oleanolic acid (OA). METHODS: The activity of UA and OA against Mycobacterium tuberculosis H37Rv, four monoresistant strains, and two drug-resistant clinical isolates were determined by MABA test. The intracellular activity of UA and OA against M. tuberculosis H37Rv and a MDR clinical isolate were evaluated in a macrophage cell line. Finally, the antitubercular activity of UA and OA was tested in BALB/c mice infected with M. tuberculosis H37Rv or a MDR strain, by determining pulmonary bacilli loads, tissue damage by automated histomorphometry, and expression of IFN-γ, TNF-α, and iNOS by quantitative RT-PCR. RESULTS: The in vitro assay showed that the UA/OA mixture has synergistic activity. The intracellular activity of these compounds against M. tuberculosis H37Rv and a MDR clinical isolate in a macrophage cell line showed that both compounds, alone and in combination, were active against intracellular mycobacteria even at low doses. Moreover, when both compounds were used to treat BALB/c mice with TB induced by H37Rv or MDR bacilli, a significant reduction of bacterial loads and pneumonia were observed compared to the control. Interestingly, animals treated with UA and OA showed a higher expression of IFN-γ and TNF-α in their lungs, than control animals. CONCLUSION: UA and OA showed antimicrobial activity plus an immune-stimulatory effect that permitted the control of experimental pulmonary TB.

Immunomodulatory Activity of Diterpenes over Innate Immunity and Cytokine Production in a Human Alveolar Epithelial Cell Line Infected with Mycobacterium tuberculosis.

BACKGROUND: Mexico has the largest number of the genus salvia plant species, whose main chemical compounds of this genus are diterpenes, these chemical compounds have shown important biological activities such as: antimicrobial, anti-inflammatory and immunomodulatory. OBJECTIVE: This study aimed to evaluate the immunomodulatory activity of three diterpenes: 1) icetexone, 2) anastomosine and 3) 7,20-dihydroanastomosine, isolated from Salvia ballotiflora, over innate immunity and cytokine production in a human alveolar epithelial cell line infected with Mycobacterium tuberculosis. METHODS: The immunomodulatory activity of diterpenes over innate immunity included reactive oxygen and nitrogen species (ROS and RNS) induction in response to infection; cytokine production included TNF-α and TGF-ß induction in response to infection. RESULTS: The diterpenes anastomosine and 7,20-dihydroanastomosine showed a statically significant (p < 0.01) increase of RNS after 36 h of infection and treatment of 2.0 µg/mL. Then, the ROS induction in response to infection showed a consistent statically significant (p < 0.01) increase after 12 h of diterpenes treatments. The cell cultures showed an anti-inflammatory effect, in the case of TGF-ß induction, in response to infection when treated with the diterpenes. On the other hand, there was not any significant effect on TNF-α release. CONCLUSION: The diterpenes anastomosine and 7,20-dihydroanastomosine increased the production of RNS after 36 h of infection and treatment. Besides, the three diterpenes increased the production of ROS after 12 h. This RNS and ROS modulation can be considered as an in vitro correlation of innate immunity in response to Mycobacterium tuberculosis infection; and an indicator of the damage of epithelial lung tissue. This study also showed an anti-inflammatory immune response by means of TGF-ß modulation when compared with control group.

Macropinocytosis is responsible for the uptake of pathogenic and non-pathogenic mycobacteria by B lymphocytes (Raji cells).

BACKGROUND: The classical roles of B cells include the production of antibodies and cytokines and the generation of immunological memory, these being key factors in the adaptive immune response. However, their role in innate immunity is currently being recognised. Traditionally, B cells have been considered non-phagocytic cells; therefore, the uptake of bacteria by B cells is not extensively documented. In this study, we analysed some of the features of non-specific bacterial uptake by B lymphocytes from the Raji cell line. In our model, B cells were infected with Mycobacterium tuberculosis (MTB), Mycobacterium smegmatis (MSM), and Salmonella typhimurium (ST). RESULTS: Our observations revealed that the Raji B cells were readily infected by the three bacteria that were studied. All of the infections induced changes in the cellular membrane during bacterial internalisation. M. smegmatis and S. typhimurium were able to induce important membrane changes that were characterised by abundant filopodia and lamellipodia formation. These membrane changes were driven by actin cytoskeletal rearrangements. The intracellular growth of these bacteria was also controlled by B cells. M. tuberculosis infection also induced actin rearrangement-driven membrane changes; however, the B cells were not able to control this infection. The phorbol 12-myristate 13-acetate (PMA) treatment of B cells induced filopodia and lamellipodia formation, the production of spacious vacuoles (macropinosomes), and the fluid-phase uptake that is characteristic of macropinocytosis. S. typhimurium infection induced the highest fluid-phase uptake, although both mycobacteria also induced fluid uptake. A macropinocytosis inhibitor such as amiloride was used and abolished the bacterial uptake and the fluid-phase uptake that is triggered during the bacterial infection. CONCLUSIONS: Raji B cells can internalise S. typhimurium and mycobacteria through an active process, such as macropinocytosis, although the resolution of the infection depends on factors that are inherent in the virulence of each pathogen.

Antiprotozoal and Antimycobacterial Activities of Pure Compounds from Aristolochia elegans Rhizomes.

We analyzed the antimycobacterial activity of the hexane extract of rhizomes from Aristolochia elegans. Some compounds of this extract were purified and tested against a group of drug-resistant Mycobacterium tuberculosis strains. We also evaluated their antiprotozoal activities. The hexane extract was active against M. tuberculosis H37Rv at a MIC = 100 µg mL(-1); the pure compounds eupomatenoid-1, fargesin, and (8R,8'R,9R)-cubebin were active against M. tuberculosis H37Rv (MIC = 50 µg mL(-1)), while fargesin presented activity against three monoresistant strains of M. tuberculosis H37Rv and a MDR clinical isolate of M. tuberculosis (MIC < 50 µg mL(-1)). Both the extract and eupomatenoid-1 were very active against E. histolytica and G. lamblia (IC(50) < 0.624 µg mL(-1)); in contrast, fargesin and (8R,8'R,9R)-cubebin were moderately active (IC(50) < 275 µg mL(-1)). In this context, two compounds responsible for the antimycobacterial presented by A. elegans are fargesin and cubebin, although others may exert this activity also. In addition to the antimycobacterial activity, the hexane extract has important activity against E. histolytica and G. lamblia, and eupomatenoid-1 is one of the compounds responsible for the antiparasite activity.

Enzymatic reduction of 9-methoxytariacuripyrone by Saccharomyces cerevisiae and its antimycobacterial activity.

Biotransformation processes have been successfully utilized to obtain products of pharmaceutical, chemical, food, and agricultural interest, which are difficult to obtain by classic chemical methods. The compound with antituberculous activity, 9-methoxy-tariacuripyrone (1), isolated from Aristolochia brevipes, was submitted to biotransformation with the yeast Saccharomyces cerevisiae under culture, yielding 5-amino-9-methoxy-3,4-dihydro-2H-benzo[h]chromen-2-one (2). The structure of (2) was elucidated on the basis of spectroscopic analyses. The results mainly show the reduction of the double bond and the nitro group of compound (1). Metabolite (2) demonstrated an increase in anti-tuberculous activity (MIC = 3.12 µg/mL) against the drug-sensitive Mycobacterium tuberculosis (H37Rv) strain, with respect to that shown by (1).

Keratinocyte Response to Infection with Sporothrix schenckii.

Sporotrichosis is a subacute, or chronic mycosis caused by traumatic inoculation of material contaminated with the fungus Sporothrix schenckii which is part of the Sporothrix spp. complex. The infection is limited to the skin, although its progression to more severe systemic or disseminated forms remains possible. Skin is the tissue that comes into contact with Sporothrix first, and the role of various cell lines has been described with regard to infection control. However, there is little information on the response of keratinocytes. In this study, we used the human keratinocyte cell line (HaCaT) and evaluated different aspects of infection from modifications in the cytoskeleton to the expression of molecules of the innate response during infection with conidia and yeast cells of Sporothrix schenckii. We found that during infection with both phases of the fungus, alterations of the actin cytoskeleton, formation of membrane protuberances, and loss of stress fibers were induced. We also observed an overexpression of the surface receptors MR, TLR6, CR3 and TLR2. Cytokine analysis showed that both phases of the fungus induced the production of elevated levels of the chemokines MCP-1 and IL-8, and proinflammatory cytokines IFN-α, IFN-γ and IL-6. In contrast, TNF-α production was significant only with conidial infection. In late post-infection, cytokine production was observed with immunoregulatory activity, IL-10, and growth factors, G-CSF and GM-CSF. In conclusion, infection of keratinocytes with conidia and yeast cells of Sporothrix schenckii induces an inflammatory response and rearrangements of the cytoskeleton.

Heat shock protein 60 from Klebsiella pneumoniae protects mononuclear cells from apoptotic cell death induced by dexamethasone.

AIMS: Bacterial heat shock proteins can have anti-apoptotic effects on human cells. We investigated whether enterobacterial HSP60 can protect peripheral blood mononuclear cells (PBMC) from DXM-induced apoptosis and if this effect requires cytoskeleton participation. MAIN METHODS: Anti-apoptotic effect from enterobacterial HSP60 was analyzed by adding these proteins to peripheral mononuclear cells cultures before DXM induction. Percentage of apoptotic cells was determined by SubG0 peak and TUNEL techniques in a flow cytometer. KEY FINDINGS: Our results showed significant protective effect of HSP60 Klebsiella pneumoniae and E. coli, in the DXM-induced apoptosis in PBMC. Similar results were obtained with recombinant human HSP60. The same protective effect of proteins was observed in CD4+ and CD8 + T cell subpopulations. To analyze if enterobacterial HSP60 need internalization to have the anti-apoptotic effect, we used cytoskeleton inhibitors such as: nocodazole, cytochalasin D and amiloride, the three inhibitors significantly affected the protective role of HSP60 in apoptosis induced with DXM. Results suggest that the protective effect of HSP60 K. pneumoniae and E. coli requires the participation of contractile structures for the internalization of this protein by the cells, we suggest that the internalization of enterobacterial HSP60 could be carry out by macropinocytosis. SIGNIFICANCE: We report for the first time that K. pneumoniae and E. coli HSP60 have protective effect in the apoptosis induced with DXM in PBMC from healthy subjects and that this effect requires the internalization of the protein with active participation of the cytoskeleton.

Antibacterial activity of Aristolochia brevipes against multidrug-resistant Mycobacterium tuberculosis.

The increased incidence of Multidrug-Resistant Mycobacterium tuberculosis (MDR-MT) requires the search for alternative antimycobacterial drugs. The main aim of this study was to evaluate the dichloromethane extract from Aristolochia brevipes (Rhizoma) and the compounds isolated from this extract against several mycobacterial strains, sensitive, resistant (monoresistant), and clinical isolates (multidrug-resistant), using the alamarBlue™ microassay. The extract was fractionated by column chromatography, yielding the following eight major compounds: (1) 6α-7-dehydro-N-formylnornantenine; (2) E/Z-N-formylnornantenine; (3) 7,9-dimethoxytariacuripyrone; (4) 9-methoxy-tariacuripyrone; (5) aristololactam I; (6) ß-sitosterol; (7) stigmasterol; and (8) 3-hydroxy-α-terpineol. The structures of these compounds were elucidated by 1H- and 13C- (1D and 2D) Nuclear Magnetic Resonance (NMR) spectroscopy. This study demonstrates that the dichloromethane extract (rhizome) of A. brevipes possesses strong in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv (Minimum Inhibitory Concentration value [MIC], 12.5 µg/mL). The most active compound against all mycobacterial strains tested was the compound aristolactam I (5), with MIC values ranging between 12.5 and 25 µg/mL. To our knowledge, this the first report of antimycobacterial activity in this plant.

[Nanoparticles as drug transporters: a promising tool against tuberculosis]. / Nanopartículas como transportadores de fármacos: una herramienta prometedora contra la tuberculosis.

The World Health Organization (WHO) places Tuberculosis (TB) as one of the most important health problems today. According to the WHO, this disease requires novel actions to control its expansion and, in this way, achieve one of the goals established in the sustainable development goals: to reduce TB morbidity and incidence by 2030 and regain control. To achieve this goal, the tools currently used for diagnosis and treatment are no longer adequate. In this sense, it is necessary to develop new drugs and vaccines, as well as novel drug administration procedures that generate a better response, reduce times, and optimize treatments. Nanotechnology has incorporated in recent years a considerable number of new tools that significantly increase the diversity of mechanisms for the administration of anti-tuberculosis drugs. Therefore, the present review briefly describes the current state of drug resistance in tuberculosis, as well as the general characteristics of nanoparticles being evaluated as tools to transport new antibiotics against tuberculosis.

La Organización Mundial de la Salud (OMS) ubica a la tuberculosis (TB) como uno de los problemas de salud más preocupantes en la actualidad, y señala que se requieren de acciones novedosas para controlar su expansión y, de esta manera, alcanzar una de las metas establecidas en los Objetivos de Desarrollo Sostenible: reducir para 2030 la morbilidad e incidencia de TB. Para lograr este objetivo, está claro que las herramientas empleadas actualmente para su diagnóstico y tratamiento ya no son las adecuadas. En este sentido, es necesario desarrollar nuevos medicamentos y vacunas, así como novedosos procedimientos de administración de fármacos que generen una mejor respuesta, disminuyan el tiempo y optimicen los tratamientos. La nanotecnología ha incorporado en los últimos años un gran número de nuevas herramientas que incrementan considerablemente, la diversidad de mecanismos para la administración de tratamientos antituberculosos. Dicho esto, la presente revisión describe brevemente el estado actual de la farmacorresistencia en TB, así como las características generales de las nanopartículas que están evaluándose como herramientas para transportar antibióticos antituberculosos.

Bacillus licheniformis and Bacillus subtilis, Probiotics That Induce the Formation of Macrophage Extracellular Traps.

Probiotics are considered living microorganisms that help preserve the health of the host who uses them. Bacillus are a genus of Gram-positive bacteria used as probiotics for animal and human consumption. They are currently distributed in various commercial forms. Two of the species used as probiotics are B. licheniformis and B. subtilis. Macrophages are central cells in the immune response, being fundamental in the elimination of microbial pathogens, for which they use various mechanisms, including the formation of extracellular traps (METs). There have been very few studies carried out on the participation of macrophages in response to the interaction of probiotics of the genus Bacillus with the host. In this work, we used macrophages from the J774A mouse cell line.1, and we found that they are susceptible to infection by the two Bacillus species. However, both species were eliminated as the infection progressed. Using confocal microscopy, we identified the formation of METs from the first hours of infection, which were characterized by the presence of myeloperoxidase (MPO) and citrullinated histone (Hit3Cit). Quantitative data on extracellular DNA release were also obtained; release was observed starting in the first hour of infection. The induction of METs by B. licheniformis caused a significant decrease in the colony-forming units (CFU) of Staphylococcus aureus. The induction of METS by bacteria of the Bacillus genus is a mechanism that participates in controlling the probiotic and potentially pathogenic bacteria such as S. aureus. The induction of METs to control pathogens may be a novel mechanism that could explain the beneficial effects of probiotics of the genus Bacillus.

Antimycobacterial neolignans isolated from Aristolochia taliscana.

Tuberculosis (TB - Mycobacterium tuberculosis) is an ancient infectious disease that has appeared once again as a serious worldwide health problem and now comprises the second leading cause of death resulting from a single infection. The prevalence of multidrug resistance (MDR) TB is increasing and therapeutic options for treatment are not always accessible; in fact, some patients do not respond to the available drugs. Therefore, there is an urgent need to develop novel anti-TB agents. The aim of the present study was to screen extracts of Aristolochia taliscana, a plant used in traditional Mexican medicine to treat cough and snake bites, for antimycobacterial activity. The hexanic extract of A. taliscana was tested by microdilution alamar blue assay against Mycobacterium strains and bioguided fractionation led to the isolation of the neolignans licarin A, licarin B and eupomatenoid-7, all of which had antimycobacterial activity. Licarin A was the most active compound, with minimum inhibitory concentrations of 3.12-12.5 microg/mL against the following M. tuberculosis strains: H37Rv, four mono-resistant H37Rv variants and 12 clinical MDR isolates, as well as against five non-tuberculous mycobacteria (NTM) strains. In conclusion, licarin A represents a potentially active anti-TB agent to treat MDR M. tuberculosis and NTM strains.