Transmission of NDM-5-Producing and OXA-48-Producing Escherichia coli Sequence Type 648 by International Visitors without Previous Medical Exposure

Although patients with history of international hospitalization are often subject to screening for multidrug-resistant organisms, it is unclear whether patients who reside in countries where carbapenemase-producing Enterobacterales (CPE) is endemic but have no history of local hospitalization contribute to the transmission of CPE. In this study, NDM-5-producing and OXA-48-producing Escherichia coli sequence type (ST) 648, a recently recognized high-risk, multidrug-resistant clone, were detected from two overseas visitors without previous medical exposure.

Arrangements of Mobile Genetic Elements among Virotype E Subpopulation of Escherichia coli Sequence Type 131 Strains with High Antimicrobial Resistance and Virulence Gene Content

Escherichia coli sequence type 131 (ST131) is a globally dominant multidrug-resistant clone that is commonly associated with extraintestinal infections. Specific sublineages have been shown to have emerged and spread within ST131, highlighting the complex nature of ST131 epidemiology.

Metronomic Chemotherapy Modulates Clonal Interactions to Prevent Drug Resistance in Non-Small Cell Lung Cancer

Despite recent advances in deciphering cancer drug resistance mechanisms, relapse is a widely observed phenomenon in advanced cancers, mainly due to intratumor clonal heterogeneity. How tumor clones progress and impact each other remains elusive. In this study, we developed 2D and 3D non-small cell lung cancer co-culture systems and defined a phenomenological mathematical model to better understand clone dynamics. Our results demonstrated that the drug-sensitive clones inhibit the proliferation of the drug-resistant ones under untreated conditions. Model predictions and their experimental in vitro and in vivo validations indicated that a metronomic schedule leads to a better regulation of tumor cell heterogeneity over time than a maximum-tolerated dose schedule, while achieving control of tumor progression. We finally showed that drug-sensitive and -resistant clones exhibited different metabolic statuses that could be involved in controlling the intratumor heterogeneity dynamics. Our data suggested that the glycolytic activity of drug-sensitive clones could play a major role in inhibiting the drug-resistant clone proliferation. Altogether, these computational and experimental approaches provide foundations for using metronomic therapy to control drug-sensitive and -resistant clone balance and highlight the potential of targeting cell metabolism to manage intratumor heterogeneity.

Different polyphenolic parenchyma cell and phloem axial resin duct-like structures formation rates in Cupressus sempervirens clones infected with Seiridium cardinale

The aim of this study was the characterization of constitutive and induced defence mechanisms in the bark tissues of Cupressus sempervirens before and after infection with the bark fungus Seiridium cardinale that is responsible for Cypress Canker Disease. The time-course development of polyphenolic parenchyma cells (PP cells) and phloem axial resin ducts PARDs(PARD) like structures) in the phloem was investigated in two C. sempervirens clones, one resistant and one susceptible to the disease, through anatomycal and hystologycal observations carried out by light microscope during a 19 days trial. PP cells were constitutively more abundant in the canker resistant clone compared to the susceptible clone, while PARDsPARD-like structures were not present in the bark of untreated plants of both clones. PP cells increased in both clones as a response to infection, but in the resistant clone they were more abundant 5 and 12 days after inoculation. Following inoculation, PARDsPARD-like structures appeared in the phloem after 5 days in the resistant clone and only after 12 days in the susceptible clone. Even the number of secretory cells (surrounding the PARDsPARD-like structures) was higher in the R clone 5 and 12 days after inoculation compared to the S clone. These observations demonstrate a faster phloem response of the resistant clone in the early phase of the infection. This may slow down initial growth of the fungus contributing to the resistance mechanism.

Starch Catabolism Revealed during Secondary Metabolite Released Under Vascular Streak Dieback Infections in Cocoa (Theobroma cacao L)

This study aimed to study the profile of starch content in cocoa leaf and phytoalexin production based on GC-MS analysis at several stages of VSD pathogen infection. Research was conducted on January – October 2015 at Kaliwining Experimental Field, Indonesian Coffee and Cocoa Research Institute, Jember, East Java. The research was designed based on a Completely Randomized Block Design with two factors with three replications. The first factor was clone, i.e. the resistant clone (Scavina 6) and susceptible (TSH 858) to VSD infection. The second factor was the level of O. theobromae infection, i.e. pre-infection, early infection, and late infection. Starch catabolism revealed during Vascular Streak Dieback infections in Cacao. Starch content in Sca 6 (resistant clone) in late infection decreased 24,33 % than healthy condition (no infection), however, starch content in TSH 858 (succeptible clone) in late infection decreased only 9,63 % than healthy condition (no infection). This indicated that starch catabolism rate on resistant clone was higher than susceptible clone. Some secondary metabolites releases under Vascular Streak Dieback i.e. I-limonene, eugenol and coumaran. Scavina 6 (resistant clone) had higher concentration of eugenol and coumaran than TSH 858 (susceptible clone). I-limonene compound, TSH 858 (Susceptible clone) had higher concentration than Scavina 6. I-Limonene concentration increased in lined with the severity of pathogen infection. There were an negative correlation between starch content with contentration of I-limonene (R= - 0,74), concentration of Eugenol (R= - 0,44), and contentration of Coumaran.

Molecular Analysis of Polymyxin Resistance among Carbapenemase-Producing Klebsiella pneumoniae in Colombia

Polymyxin resistance in Klebsiella pneumoniae has been attributed to mutations in mgrB, phoPQ, pmrAB, and crrAB and to the presence of mcr plasmid-mediated genes. Herein, we describe the molecular characteristics of 24 polymyxin- and carbapenem-resistant K. pneumoniae isolates recovered from six Colombian cities between 2009 and 2019. Minimum inhibitory concentrations (MICs) to polymyxin were confirmed by broth microdilution, and whole-genome sequencing was performed to determine sequence type, resistome, and mutations in the genes related to polymyxin resistance, as well the presence of mcr. The results showed high-level resistance to polymyxin (MICs ≥ 4 μg/mL). blaKPC-3 was present in the majority of isolates (17/24; 71%), followed by blaKPC-2 (6/24; 25%) and blaNDM-1 (1/24; 4%). Most isolates belonged to the CG258 (17/24; 71%) and presented amino acid substitutions in PmrB (22/24; 92%) and CrrB (15/24; 63%); mutations in mgrB occurred in only five isolates (21%). Additional mutations in pmrA, crrA, and phoPQ nor any of the mcr resistance genes were identified. In conclusion, we found clonal dissemination of polymyxin and carbapenem-resistant K. pneumoniae isolates in Colombia, mainly associated with CG258 and blaKPC-3. Surveillance of this multidrug-resistant clone is warranted due to the limited therapeutic options for the treatment of carbapenem-resistant K. pneumoniae infections.

New 4-aminoquinolines as moderate inhibitors of P. falciparum malaria

Synthesis of novel aminoquinoline derivatives has been accomplished and their activity against malaria strains has been examined. The compounds showed moderate in vitro antimalarial activity against two P. falciparum strains, 3D7 (CQ susceptible clone) and Dd2 (CQ resistant clone). Three amino-quinolines were further examined for antimalarial efficacy in a mouse model using a modified Thompson test. In this model, mice were infected with P. berghei-infected red blood cells, and drugs were administered orally. Anti-malarial 3 was found toxic at a dose of 320 (mg/kg)/day in 3/6 mice, however, 2/6 mice of the same group survived through day 31, and one of them was cured.

Evolution of ST-4821 clonal complex hyperinvasive and quinolone-resistant meningococci: the next meningococcal pandemic?

The expansion of quinolone-resistant Neisseria meningitidis clone ChinaCC4821-R1-C/B from ST-4821 clonal complex (cc4821) caused a serogroup shift from serogroup A to C in invasive meningococcal disease (IMD) in China. To establish the relationship among globally distributed cc4821 meningococci, we analysed whole genome sequence data from 173 cc4821 meningococci isolated in four continents from 1972-2019. These meningococci clustered into four sub-lineages (1-4), with sub-lineage 1 primarily comprising serogroup C IMD isolates (82%, 41/50). Most isolates from outside China formed a distinct sub-lineage (81.6%, 40/49, the Europe-USA cluster), with the typical strain designation B:P1.17-6,23:F3-36:ST-3200(cc4821) and harbouring mutations in penicillin-binding protein 2. These data show that the quinolone-resistant clone ChinaCC4821-R1-C/B has expanded to other countries. The increasing global distribution of B:cc4821 meningococci raises concern that cc4821 has the potential to cause a global pandemic and, this would be challenging to control though there is indirect evidence that Trumenba® vaccine might afford some protection.

Terpenoid Accumulation Links Plant Health and Flammability in the Cypress-Bark Canker Pathosystem

To explore the possible relationship between diseased trees and wildfires, we assessed the flammability of canker-resistant and susceptible common cypress clones that were artificially infected with Seiridium cardinale compared to healthy trees. This study explored the effect of terpenoids produced by the host plant in response to infection and the presence of dead plant portions on flammability. Terpenoids were extracted and quantified in foliage and bark samples by gas chromatography–mass spectrometry (GC–MS). A Mass Loss Calorimeter was used to determine the main flammability descriptors. The concentration of terpenoids in bark and leaf samples and the flammability parameters were compared using a generalized linear mixed models (GLMM) model. A partial least square (PLS) model was generated to predict flammability based on the content of terpenoid, clone response to bark canker and the disease status of the plants. The total terpenoid content drastically increased in the bark of both cypress clones after infection, with a greater (7-fold) increase observed in the resistant clone. On the contrary, levels of terpenoids in leaves did not alter after infection. The GLMM model showed that after infection, plants of the susceptible clone appeared to be much more flammable in comparison to those of resistant clones, showing higher ignitability, combustibility, sustainability and consumability. This was mainly due to the presence of dried crown parts in the susceptible clone. The resistant clone showed a slightly higher ignitability after infection, while the other flammability parameters did not change. The PLS model (R2Y = 56%) supported these findings, indicating that dead crown parts and fuel moisture content accounted for most of the variation in flammability parameters and greatly prevailed on terpenoid accumulation after infection. The results of this study suggest that a disease can increase the flammability of trees. The deployment of canker-resistant cypress clones can reduce the flammability of cypress plantations in Mediterranean areas affected by bark canker. Epidemiological data of diseased tree distribution can be an important factor in the prediction of fire risk.