Potential Anti-Infectious Activity of Essential Oil Chemotypes of Lippia origanoides Kunth on Antibiotic-Resistant Staphylococcus aureus Strains.

Staphylococcus aureus infections are prevalent in healthcare and community environments. Methicillin-resistant S. aureus is catalogued as a superbug of high priority among the pathogens. This Gram-positive coccus can form biofilms and produce toxins, leading to persistent infection and antibiotic resistance. Limited effective antibiotics have encouraged the development of innovative strategies, with a particular emphasis on resistance mechanisms and/or virulence factors. Medicinal aromatic plants have emerged as promising alternative sources. This study investigated the antimicrobial, antibiofilm, and antihemolysis properties of three different chemotypes of Lippia origanoides essential oil (EO) against susceptible and drug-resistant S. aureus strains. The chemical composition of the EO was analyzed using GC-MS, revealing high monoterpene concentrations, with carvacrol and thymol as the major components in two of the chemotypes. The third chemotype consisted mainly of the sesquiterpene ß-caryophyllene. The MIC values for the two monoterpene chemotypes ranged from 62.5 to 500 µg/mL for all strains, whereas the sesquiterpene chemotype showed activity against seven strains at concentrations of 125-500 µg/mL, which is the first report of its anti-S. aureus activity. The phenolic chemotypes inhibited biofilm formation in seven S. aureus strains, whereas the sesquiterpene chemotype only inhibited biofilm formation in four strains. In addition, phenolic chemotypes displayed antihemolysis activity, with IC50 values ranging from 58.9 ± 3.8 to 128.3 ± 9.2 µg/mL. Our study highlights the importance of L. origanoides EO from the Yucatan Peninsula, which has the potential for the development of anti-S. aureus agents.

[Gram-negative bacteria of critical priority in ICU patients from a tertiary care hospital]. / Bacterias Gram-negativas de prioridad crítica en pacientes de las UCI de un hospital de tercer nivel.

Background: Intensive care units (ICU) are the epicenter of antimicrobial resistance (AMR), and patients' infections are mainly caused by Gram-negative bacteria (GNB). Objective: To describe the frequency and trends in AMR of GNB deriving from the clinical samples of ICU patients at a tertiary care hospital in Mérida, Yucatán. Material and methods: Study which included the review of laboratory reports of all bacteriological samples collected from patients admitted to neonatal, pediatric and adult ICU from January 1 2019 to December 31 2021. Results: 433 GNB isolates were recovered, with Klebsiella pneumoniae being the most predominant isolate (n = 117; 27.02%). The majority of GNB were recovered from bronchial secretions (n = 163). Overall, GNB showed high resistance rates to ampicillin (89.48%), ampicillin/sulbactam (66.85%), cephalosporins (58.52-93.81%), tobramycin (58.06%), and tetracycline (61.73%). Among GNB, 73.90% and 68.53% exhibited multidrug-resistant, and highly resistant microorganisms' profiles, respectively, and 47.54% of Acinetobacter baumannii exhibited an extensively drug-resistant profile. A total of 80.33% of A. baumannii was carbapenem-resistant, and 83.76% of K. pneumoniae strains were ESBL-producing. Conclusion: Our data could be helpful to improve the empirical therapy and the infection-control program.

Introducción: las unidades de cuidados intensivos (UCI) son el epicentro de la resistencia a los antimicrobianos (RAM) y las infecciones en estas áreas son causadas principalmente por bacterias Gram-negativas (BGN). Objetivo: describir la frecuencia y los patrones de RAM en BGN aisladas de muestras clínicas de pacientes de las UCI de un hospital de tercer nivel en Mérida, Yucatán. Material y métodos: estudio que incluyó la revisión de los reportes de laboratorio de las muestras bacteriológicas obtenidas de pacientes ingresados en las UCI neonatal, pediátrica y adulta del 1 de enero de 2019 al 31 de diciembre de 2021. Resultados: se identificaron 433 BGN y Klebsiella pneumoniae fue el patógeno más prevalente (n = 117; 27.02%). La mayoría de las BGN aisladas se obtuvieron de secreciones bronquiales (n = 163). En general, las BGN mostraron altas tasas de resistencia a ampicilina (89.48%), ampicilina/sulbactam (66.85%), cefalosporinas (58.52-93.81%), tobramicina (58.06%) y tetraciclina (61.73%). El 73.90% y el 68.53% de las BGN exhibieron perfiles multidrogorresistentes y microorganismos altamente resistentes a fármacos, respectivamente, y 47.54% de los aislamientos de Acinetobacter baumannii mostró perfil de drogorresistencia extendida. El 80.33% de los A. baumannii fue resistente a carbapenémicos y el 83.76% de las K. pneumoniae fueron productoras de BLEE. Conclusión: nuestros datos podrían mejorar la terapia antimicrobiana empírica y el programa de control de infecciones.

Anti-Leishmania activity of the Mayan medicinal plant Thouinia paucidentata Radlk extracts.

Mexico's Yucatan Peninsula is an endemic area of cutaneous leishmaniasis, locally known as the chiclero's ulcer, and Mayan traditional medicine which refers to the use of Thouinia paucidentata Radlk, known as k'an chuunup. Aqueous and organic leaves extracts were evaluated against promastigotes and amastigotes of Leishmania mexicana. Toxicity tests of extracts were performed using Vero and J774A.1 macrophage cell lines. The composition of the most active extracts was analysed by GC-MS. The n-hexane and ethyl acetate extracts showed potent anti-Leishmania activity against the promastigote form, and remarkably, n-hexane extract exhibited potent activity against the amastigote form. Both extracts showed low toxicity on Vero both not on J774A.1 cells. Analysis of both bioactive extracts identified as more abundant compounds, germacrene D-4-ol and thunbergen in n-hexane, and thunbergol in ethyl acetate extracts. Our study presents T. paucidentata as anti-Leishmania phytomedicine supporting its medicinal use and contributes to the understanding of its phytochemical composition.

Efficacy of Fosfomycin against Planktonic and Biofilm-Associated MDR Uropathogenic Escherichia coli Clinical Isolates.

Urinary tract infections (UTI) are a severe public health problem and are caused mainly by the uropathogenic Escherichia coli (UPEC). Antimicrobial resistance and limited development of new antimicrobials have led to the reuse of old antibiotics such as fosfomycin. The aim of this study was to evaluate the in vitro efficacy of fosfomycin on a collection of multidrug-resistant (MDR) UPEC and the degradative activity on biofilm producers. A total of 100 MDR UPEC clinical isolates were collected from patients at Mexican second- and third-level hospitals. Microorganism identification was performed using an automated system, the evaluation of the susceptibility of clinical isolates to fosfomycin was performed using the resazurin microtiter assay, and the identification of biofilm producers and the effect of fosfomycin in biofilms were evaluated using the crystal violet method. Among planktonic MDR UPEC, 93% were susceptible to fosfomycin. Eighty-three MDR UPEC were categorized as weak (39.8%), moderate (45.2%), and strong (14.5%) biofilm producers. Fosfomycin exhibited degradative activity ranging from 164.4 µg/mL to 1045 µg/mL. Weak producers required statistically lower concentrations of fosfomycin to destroy the biofilm, contrary to moderate and strong producers. In conclusion, fosfomycin could be an option for the treatment of infections caused by MDR UPEC, for which the antimicrobial treatment is more often becoming limited.

Activity of Semi-Synthetic Mulinanes against MDR, Pre-XDR, and XDR Strains of Mycobacterium tuberculosis.

Tuberculosis causes more than 1.2 million deaths each year. Worldwide, it is the first cause of death by a single infectious agent. The emergence of drug-resistant strains has limited pharmacological treatment of the disease and today, new drugs are urgently needed. Semi-synthetic mulinanes have previously shown important activity against multidrug-resistant (MDR) Mycobacterium tuberculosis. In this investigation, a new set of semi-synthetic mulinanes were synthetized, characterized, and evaluated for their in vitro activity against three drug-resistant clinical isolates of M. tuberculosis: MDR, pre-extensively Drug-Resistant (pre-XDR), and extensively Drug-Resistant (XDR), and against the drug-susceptible laboratory reference strain H37Rv. Derivative 1a showed the best anti-TB activity (minimum inhibitory concentration [MIC] = 5.4 µM) against the susceptible strain and was twice as potent (MIC = 2.7 µM) on the MDR, pre-XDR, and XDR strains and also possessed a bactericidal effect. Derivative 1a was also tested for its anti-TB activity in mice infected with the MDR strain. In this case, 1a produced a significant reduction of pulmonary bacilli loads, six times lower than the control, when tested at 0.2536 mg/Kg. In addition, 1a demonstrated an adjuvant effect by shortening second-line chemotherapy. Finally, the selectivity index of >15.64 shown by 1a when tested on Vero cells makes this derivative an important candidate for future studies in the development of novel antitubercular agents.

Antibacterial and antibiofilm activities of Mayan medicinal plants against Methicillin-susceptible and -resistant strains of Staphylococcus aureus.

ETHNOPHARMACOLOGICAL RELEVANCE: Several medicinal plants are used in Mayan Traditional Medicine to treat skin, urinary, respiratory, and gastrointestinal infectious diseases. However, scientific studies that have supported the bioactivity of these Mayan medicinal plants are limited. AIM OF THE STUDY: To assess the in-vitro anti-Staphylococcus aureus growth and biofilm-formation activities of 15 Mayan medicinal plants that were selected based on their traditional uses for the treatment of infectious diseases. MATERIALS AND METHODS: Mayan medicinal plants used traditionally to treat infectious diseases were preselected. For each part of the plants, four extracts were prepared with different solvents (water, n-hexane, ethyl acetate, and methanol). These were tested against two reference strains: a Methicillin-susceptible and -resistant S. aureus, and two clinical isolates, including a susceptible and multidrug-resistant S. aureus using a Resazurin Microtiter Assay. In addition, the plant extracts were evaluated in biofilm-formation inhibition on S. aureus by means of the Crystal Violet method. RESULTS: A total of 120 extracts from 15 Mayan medicinal plant species belonging to 12 different families were selected according their ethnopharmacological uses to treat infectious diseases. Among the selected plant species, 26 extracts obtained from eight medicinal Mayan plants exhibited significant anti-S. aureus against the four strains tested. The most active extracts were the Aq (aqueous) leaf extract of Krugiodendron ferreum (Minimal Inhibitory Concentration [MIC] = 125-250 µg/mL), the MeOH bark extracts of Matayba oppositifolia, Clusia flava, Gymnopodium floribundum, the MeOH leaf extract of Spondias purpurea with MIC values of 250 µg/mL, and the MeOH leaf and Aq bark extracts of K. ferreum (MIC = 250-500 µg/mL). Among the active extracts, 12 exhibited a bactericidal effect on S. aureus strains (Minimal Bactericidal Concentration [MBC] = 250-1000 µg/mL). Forty extracts from 13 plants have an effect on the anti-formation of biofilm, the most active were the MeOH leaf extract of M. oppositifolia (one-half Inhibitory Concentration [IC50] = 10.4 µg/mL) and the MeOH (IC50 = 17.7 µg/mL) and Hex (18.2 µg/mL) leaf extracts from S. purpurea. CONCLUSION: Aqueous and organic extracts from Mayan medicinal plants showed bactericidal and anti-biofilm activities even against drug-resistant S. aureus strains. The present study supports the traditional usage of some plants employed in Mayan medicine for illnesses such as skin, gastrointestinal, and urinary infections and suggest that these plants could be a good source of antibacterial phytochemicals.

Mulinane- and Azorellane-Type Diterpenoids: A Systematic Review of Their Biosynthesis, Chemistry, and Pharmacology.

Mulinane- and azorellane-type diterpenoids have unique tricyclic fused five-, six-, and seven-membered systems and a wide range of biological properties, including antimicrobial, antiprotozoal, spermicidal, gastroprotective, and anti-inflammatory, among others. These secondary metabolites are exclusive constituents of medicinal plants belonging to the Azorella, Laretia, and Mulinum genera. In the last 30 years, more than 95 mulinanes and azorellanes have been reported, 49 of them being natural products, 4 synthetics, and the rest semisynthetic and biotransformed derivatives. This systematic review highlights the biosynthetic origin, the chemistry, and the pharmacological activities of this remarkably interesting group of diterpenoids.

In vitro growth inhibition and bactericidal activity of spathulenol against drug-resistant clinical isolates of Mycobacterium tuberculosis

ABSTRACT Spathulenol was isolated from an extract of Azorella compacta Phil., Apiaceae, by various chromatographic method; identification of the chemical structure was confirmed by comparing its spectroscopic data with those reported in the literature. The anti-Mycobacterium tuberculosis activity of spathulenol was evaluated on MDR, pre-XDR, and XDR clinical isolates of M. tuberculosis, as well as on the reference susceptible strain H37Rv and its cytotoxic activity was evaluated on the Vero Cell Line. The anti-M. tuberculosis activity of spathulenol was twice as potent against the MDR, pre-XDR, and XDR clinical isolates (6.25 µg/ml) than on the susceptible H37Rv strain (12.5 µg/ml). Additionally, the anti-M. tuberculosis activity shown by spathulenol was established as bactericidal on drug-resistant and susceptible strains of M. tuberculosis. Finally, cytotoxic activity on the Vero cell line (CC50 = 95.7 µg/ml) indicated that spathulenol is a selective anti-M. tuberculosis compound, with a selective index of 15.31 against drug-resistant clinical isolates of M. tuberculosis.

Bactericidal Effect of the Leaf Extract from Musa spp. (AAB Group, Silk Subgroup), cv. "Manzano" Against Multidrug-Resistant Mycobacterium tuberculosis.

Air-dried leaves of a Musa spp. AAB, cv. "Manzano" plant, known as Ja'as in the Maya culture, were sequentially extracted with hexane, ethyl acetate, and methanol; the resulting extracts were investigated for their antimycobacterial activity against susceptible and drug-resistant strains of Mycobacterium tuberculosis (MTB) using the Microplate Alamar Blue Assay. Both the n-hexane extract (HE) and ethyl acetate extract (EE) showed potent activity against both strains of MTB, with the EE exhibiting the strongest activity and a Minimum Inhibitory Concentration of 12.5 and 6.25 µg/mL against susceptible and drug-resistant strains, respectively. Both extracts also demonstrated a mycobactericidal effect and a very good selectivity index when tested for cytotoxic activity on Vero monkey kidney cells, using the Sulforhodamine B assay. Our results demonstrate the efficiency and selectivity of Musa spp. AAB, cv. "Manzano" against MTB strains and support its traditional use as remedy against tuberculosis in Maya traditional medicine.