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Patel, A.

Publications and source records attributed to Patel, A..

At least 91 records · Page 5Linked to original sources

Performance of Large Language Models on Pharmacy Exam: A Comparative Assessment Using the NAPLEX

BackgroundThere has been considerable recent effort in integrating Large Language Models (LLMs) across different fields, including healthcare. However, the possibility of applying LLMs in pharmacy-related sciences is under-explored. ObjectivesThis study aims to evaluate the capabilities and limitations of six LLMs-GPT-3.5, GPT-4, Llama-2-7B, Llama-2-13B, Llama-2-70B, and Mistral-7B, in the field of pharmacy by assessing their reasoning abilities on a sample of the North American Pharmacist Licensure Examination (NAPLEX). Additionally, we explore the potential impacts of LLMs on pharmacy education and practice. MethodsTo evaluate the LLMs, we utilized the sample of the NAPLEX exam comprising 225 multiple-choice questions sourced from the APhA Complete Review for Pharmacy, 13th Edition | Pharmacy Library. These questions were presented to the Large Language Models through either local deployment or the Application programming interface (API), and the answers generated by the LLMs were subsequently compared with the answer key. ResultsThere is a notable disparity in the performance of the LLMs. GPT-4 emerged as the top performer, accurately answering 87.1% of the questions. Among the six LLMs evaluated, GPT-4 was the only model capable of passing the NAPLEX exam. ConclusionWe examined the performance of Large Language Models based on their model size, training methods, and fine-tuning algorithms. Given the continuous evolution of LLMs, it is reasonable to anticipate that future models will effortlessly excel in exams such as the NAPLEX. This highlights the significant potential of LLMs to influence the field of pharmacy. Hence, we must evaluate both the positive and negative implications associated with the integration of LLMs in pharmacy education and practice.

bioinformatics↗

Tradeoffs in the Design of RNA Thermometers

The synthesis of RNA thermometers is aimed at achieving temperature responses with desired thresholds and sensitivities. Although previous works have generated thermometers with a variety of thresholds and sensitivities as well as guidelines for design, possible constraints in the achievable thresholds and sensitivities remain unclear. We addressed this issue using a two-state model and its variants, as well as melt profiles generated from thermodynamic computations. In the two-state model, we found that the threshold was inversely proportional to the sensitivity, in the case of a fixed energy difference between the two states. Notably, this constraint could persist in variations of the two-state model with sequentially unfolding states and branched parallel pathways. Furthermore, the melt profiles generated from a library of thermometers exhibited a similar constraint. These results should inform the design of RNA thermometers as well as other responses that are mediated in a similar fashion.

synthetic biology↗

Cell-type-resolved somatic mosaicism reveals clonal dynamics of the human forebrain

Debate remains around anatomic origins of specific brain cell subtypes and lineage relationships within the human forebrain. Thus, direct observation in the mature human brain is critical for a complete understanding of the structural organization and cellular origins. Here, we utilize brain mosaic variation within specific cell types as distinct indicators for clonal dynamics, denoted as cell-type-specific Mosaic Variant Barcode Analysis. From four hemispheres from two different human neurotypical donors, we identified 287 and 780 mosaic variants (MVs), respectively that were used to deconvolve clonal dynamics. Clonal spread and allelic fractions within the brain reveal that local hippocampal excitatory neurons are more lineage-restricted compared with resident neocortical excitatory neurons or resident basal ganglia GABAergic inhibitory neurons. Furthermore, simultaneous genome-transcriptome analysis at both a cell-type-specific and single-cell level suggests a dorsal neocortical origin for a subgroup of DLX1+ inhibitory neurons that disperse radially from an origin shared with excitatory neurons. Finally, the distribution of MVs across 17 locations within one parietal lobe reveals restrictions of clonal spread in the anterior-posterior axis precedes that of the dorsal-ventral axis for both excitatory and inhibitory neurons. Thus cell-type resolved somatic mosaicism can uncover lineage relationships governing the development of the human forebrain.

neuroscience↗

Integrating Shear Flow and Trypsin Treatment to Assess Cell Adhesion Strength

Cell adhesion is of fundamental importance in cell and tissue organization, and for designing cell-laden constructs for tissue engineering. Prior methods to assess cell adhesion strength for strongly adherent cells using hydrodynamic shear flow either involved the use of specialized flow devices to generate high shear stress or used simpler implementations like larger height parallel plate chambers that enable multi-hour cell culture but generate low shear stress and are hence more applicable for weakly adherent cells. Here, we propose a shear flow assay for adhesion strength assessment of strongly adherent cells that employs off-the-shelf parallel plate chambers for shear flow as well as simultaneous trypsin treatment to tune down the adhesion strength of cells. We implement the assay with a strongly adherent cell type and show that shear stress in the 0.07 to 7 Pa range is sufficient to dislodge the cells with simultaneous trypsin treatment. Imaging of cells over a square centimeter area allows cell morphological analysis of hundreds of cells. We show that the cell area of cells that are dislodged, on average, does not monotonically increase with shear stress at the higher end of shear stresses used and suggest that this can be explained by the likely higher resistance of high circularity cells to trypsin digestion. The adhesion strength assay proposed can be easily adapted by labs to assess the adhesion strength of both weakly and strongly adherent cell types and has the potential to be adapted for substrate stiffness-dependent adhesion strength assessment in mechanobiology studies.

bioengineering↗

iPSC-based modeling of helicase deficiency reveals impaired cell proliferation and increased apoptosis after NK cell lineage commitment

While monogenic variants in CDC45-MCM-GINS (CMG) replisome proteins cause human natural killer cell deficiencies (NKD), family members with the same inherited variants often have variable clinical and cellular phenotypes. We investigated two siblings with inherited compound heterozygous GINS4 variants but variable disease expressivity. Cell cycle impairment and increased apoptosis were detected following NK cell lineage commitment but not in pluripotent cells. While this effect was detected in both siblings, the efficiency of NK cell differentiation was variable and correlated with differential clinical severity of NKD. Further investigation of allelic expression of inherited GINS4 variants demonstrated expected biallelic expression of GINS4 in pluripotent cells and progenitors. However, allelic bias in lineage-committed NK cells led to over- or under-representation of more damaging GINS4 heterozygous variants associated with differential cellular and clinical severity. This study identifies allelic bias that causes phenotypic variation of monogenic diseases and defines mechanisms underlying immunodeficiency.

cell biology↗

Formin tails act as a switch, inhibiting or enhancing processive actin elongation

Formins are large, multidomain proteins that nucleate new actin filaments and accelerate elongation through a processive interaction with the barbed end of filaments. Their actin assembly activity is generally attributed to their eponymous Formin Homology (FH) 1 and 2 domains; however, evidence is mounting that regions outside of the FH1FH2 stretch also tune actin assembly. Here, we explore the underlying contributions of the tail domain, which spans the sequence between the FH2 domain and the C-terminus of formins. Tails vary in length from [~]0 to >200 residues and contain a number of recognizable motifs. The most well-studied motif is the [~]15 residue long diaphanous autoregulatory domain (DAD). The DAD mediates all or nothing regulation of actin assembly through an intramolecular interaction with the diaphanous inhibitory domain (DID) in the N-terminal half of the protein. Multiple reports demonstrate that the tail can enhance both nucleation and processivity. In this study, we provide a high-resolution view of the alternative splicing encompassing the tail in the Formin Homology Domain-(Fhod) family of formins during development. While four distinct tails are predicted, we found significant levels of only two of these. We characterized the biochemical effects of the different tails. Surprisingly, the two highly expressed Fhod-tails inhibit processive elongation and diminish the nucleation and elongation rates, while a third supports activity. These findings demonstrate a new mechanism of modulating actin assembly by formins and support the model that splice variants are specialized to build distinct actin structures during development.

biochemistry↗

Phenotyping the virulence of SARS-CoV-2 variants in hamsters by digital pathology and machine learning

SARS-CoV-2 has continued to evolve throughout the COVID-19 pandemic, giving rise to multiple variants of concern (VOCs) with different biological properties. As the pandemic progresses, it will be essential to test in near real time the potential of any new emerging variant to cause severe disease. BA.1 (Omicron) was shown to be attenuated compared to the previous VOCs like Delta, but it is possible that newly emerging variants may regain a virulent phenotype. Hamsters have been proven to be an exceedingly good model for SARS-CoV-2 pathogenesis. Here, we aimed to develop robust quantitative pipelines to assess the virulence of SARS-CoV-2 variants in hamsters. We used various approaches including RNAseq, RNA in situ hybridization, immunohistochemistry, and digital pathology, including software assisted whole section imaging and downstream automatic analyses enhanced by machine learning, to develop methods to assess and quantify virus-induced pulmonary lesions in an unbiased manner. Initially, we used Delta and Omicron to develop our experimental pipelines. We then assessed the virulence of recent Omicron sub-lineages including BA.5, XBB, BQ.1.18, BA.2 and BA.2.75. We show that in experimentally infected hamsters, accurate quantification of alveolar epithelial hyperplasia and macrophage infiltrates represent robust markers for assessing the extent of virus-induced pulmonary pathology, and hence virus virulence. In addition, using these pipelines, we could reveal how some Omicron sub-lineages (e.g., BA.2.75) have regained virulence compared to the original BA.1. Finally, to maximise the utility of the digital pathology pipelines reported in our study, we developed an online repository containing representative whole organ histopathology sections that can be visualised at variable magnifications (https://covid-atlas.cvr.gla.ac.uk). Overall, this pipeline can provide unbiased and invaluable data for rapidly assessing newly emerging variants and their potential to cause severe disease.

microbiology↗

New design strategies for ultra-specific CRISPR-Cas13a-based RNA-diagnostic tools with single-nucleotide mismatch sensitivity

The pressing need for clinical diagnostics has required the development of novel nucleic acid-based detection technologies that are sensitive, fast, and inexpensive, and that can be deployed at point-of-care. Recently, the RNA-guided ribonuclease CRISPR-Cas13 has been successfully harnessed for such purposes. However, developing assays for detection of genetic variability, for example single-nucleotide polymorphisms, is still challenging and previously described design strategies are not always generalizable. Here, we expanded our characterization of LbuCas13a RNA-detection specificity by performing a combination of experimental RNA mismatch tolerance profiling, molecular dynamics simulations, protein, and crRNA engineering. We found certain positions in the crRNA-target-RNA duplex that are particularly sensitive to mismatches and establish the effect of RNA concentration in mismatch tolerance. Additionally, we determined that shortening the crRNA spacer or modifying the direct repeat of the crRNA leads to stricter specificities. Furthermore, we harnessed our understanding of LbuCas13a allosteric activation pathways through molecular dynamics and structure-guided engineering to develop novel Cas13a variants that display increased sensitivities to single-nucleotide mismatches. We deployed these Cas13a variants and crRNA design strategies to achieve superior discrimination of SARS-CoV-2 strains compared to wild-type LbuCas13a. Together, our work provides new design criteria and new Cas13a variants for easier-to-implement Cas13-based diagnostics. KEY POINTSO_LICertain positions in the Cas13a crRNA-target-RNA duplex are particularly sensitive to mismatches. C_LIO_LIUnderstanding Cas13as allosteric activation pathway allowed us to develop novel high-fidelity Cas13a variants. C_LIO_LIThese Cas13a variants and crRNA design strategies achieve superior discrimination of SARS-CoV-2 strains. C_LI GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=145 SRC="FIGDIR/small/550755v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@1a3fd63org.highwire.dtl.DTLVardef@1509a82org.highwire.dtl.DTLVardef@cfcd7aorg.highwire.dtl.DTLVardef@bb2f0f_HPS_FORMAT_FIGEXP M_FIG New strategies to improve Cas13a RNA-detection specificity developed via mismatch tolerance profiling, uncovering features that modulate specificity, and structure-guided engineering of LbuCas13a. C_FIG

molecular biology↗

Using CombiCells, a platform enabling titration and combinatorial display of cell surface ligands, to investigate the sensitivity and costimulatory requirements of TCRs and CARs

Understanding how cellular decisions by receptor/ligand interactions at cell/cell interface has been challenging because it is difficult to independently vary the surface density of multiple ligands. Here, we exploit the SpyCatcher/SpyTag split-protein system for rapid combinatorial display of native ligands on cells (Combicells). We use this platform to assess T cell antigen sensitivity and the impact of T cell co-stimulation/co-inhibition receptors. The TCR displayed much greater sensitivity to pMHC than CARs and BiTES did to CD19. While TCR sensitivity was greatly enhanced by CD2 ligand, CAR sensitivity to CD19 was primarily but more modestly enhanced by LFA-1 ligand. Lastly, we show that the PD-1/ligand engagement inhibited T cell activation triggered solely by TCR/pMHC interactions, as well as the amplified activation induced by CD2 and CD28 co-stimulation. The ability to easily produce cells with different concentrations and combinations of ligands should accelerate the study of receptor/ligand interactions at cell/cell interfaces. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=177 SRC="FIGDIR/small/545075v2_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@d1ec95org.highwire.dtl.DTLVardef@33c0forg.highwire.dtl.DTLVardef@5bfed7org.highwire.dtl.DTLVardef@1b80ee2_HPS_FORMAT_FIGEXP M_FIG C_FIG One sentence summaryUsing CombiCells, a platform for the combinatorial display of cell surface ligands, to compare T cell antigen sensitivity mediated by TCRs, CARs, and BiTEs and its dependence on co-stimulation/co-inhibition receptor ligands

immunology↗

Clinical Knowledge and Reasoning Abilities of AI Large Language Models in Pharmacy: A Comparative Study on the NAPLEX Exam

ObjectiveThis study aims to evaluate the capabilities and limitations of three large language models (LLMs) - GPT-3, GPT-4, and Bard, in the field of pharmaceutical sciences by assessing their pharmaceutical reasoning abilities on a sample North American Pharmacist Licensure Examination (NAPLEX). We also analyze the potential impacts of LLMs on pharmaceutical education and practice. MethodsA sample NAPLEX exam consisting of 137 multiple-choice questions was obtained from an online source. GPT-3, GPT-4, and Bard were used to answer the questions by inputting them into the LLMs user interface. The answers provided by the LLMs were then compared with the answer key. ResultsGPT-4 exhibited superior performance compared to GPT-3 and Bard, answering 78.8% of the questions correctly. This score was 11% higher than Bard and 27.7% higher than GPT-3. However, when considering questions that required multiple selections, the performance of each LLM decreased significantly. GPT-4, GPT-3, and Bard only correctly answered 53.6%, 13.9%, and 21.4% of these questions, respectively. ConclusionAmong the three LLMs evaluated, GPT-4 was the only model capable of passing the NAPLEX exam. Nevertheless, given the continuous evolution of LLMs, it is reasonable to anticipate that future models will effortlessly pass the exam. This highlights the significant potential of LLMs to impact the pharmaceutical field. Hence, we must evaluate both the positive and negative implications associated with the integration of LLMs in pharmaceutical education and practice.

scientific communication and education↗

DNA repair and anti-cancer mechanisms in the longest-living mammal: the bowhead whale

At over 200 years, the maximum lifespan of the bowhead whale exceeds that of all other mammals. The bowhead is also the second-largest animal on Earth, reaching over 80,000 kg1. Despite its very large number of cells and long lifespan, the bowhead is not highly cancer-prone, an incongruity termed Petos Paradox2. This phenomenon has been explained by the evolution of additional tumor suppressor genes in other larger animals, supported by research on elephants demonstrating expansion of the p53 gene3-5. Here we show that bowhead whale fibroblasts undergo oncogenic transformation after disruption of fewer tumor suppressors than required for human fibroblasts. However, analysis of DNA repair revealed that bowhead cells repair double strand breaks (DSBs) and mismatches with uniquely high efficiency and accuracy compared to other mammals. The protein CIRBP, implicated in protection from genotoxic stress, was present in very high abundance in the bowhead whale relative to other mammals. We show that CIRBP and its downstream protein RPA2, also present at high levels in bowhead cells, increase the efficiency and fidelity of DNA repair in human cells. These results indicate that rather than possessing additional tumor suppressor genes as barriers to oncogenesis, the bowhead whale relies on more accurate and efficient DNA repair to preserve genome integrity. This strategy which does not eliminate damaged cells but repairs them may be critical for the long and cancer-free lifespan of the bowhead whale.

cancer biology↗

An unsupervised learning approach uncovers divergent mesenchymal-like gene expression programs across human neuroblastoma tumors, preclinical models, and chemotherapy-exposed tumors.

Neuroblastoma is a common pediatric cancer, where preclinical studies suggest that a mesenchymal-like gene expression program contributes to chemotherapy resistance. However, clinical outcomes remain poor, implying we need a better understanding of the relationship between patient tumor heterogeneity and preclinical models. Here, we generated single-cell RNA-seq maps of neuroblastoma cell lines, patient-derived xenograft models (PDX), and a genetically engineered mouse model (GEMM). We developed an unsupervised machine learning approach ( automatic consensus nonnegative matrix factorization (acNMF)) to compare the gene expression programs found in preclinical models to a large cohort of patient tumors. We confirmed a weakly expressed, mesenchymal-like program in otherwise adrenergic cancer cells in some pre-treated high-risk patient tumors, but this appears distinct from the presumptive drug-resistance mesenchymal programs evident in cell lines. Surprisingly however, this weak-mesenchymal-like program was maintained in PDX and could be chemotherapy-induced in our GEMM after only 24 hours, suggesting an uncharacterized therapy-escape mechanism. Collectively, our findings improve the understanding of how neuroblastoma patient tumor heterogeneity is reflected in preclinical models, provides a comprehensive integrated resource, and a generalizable set of computational methodologies for the joint analysis of clinical and pre-clinical single-cell RNA-seq datasets.

cancer biology↗

Revisiting the role of Acinetobacter sp. in EBPR systems

Side-stream Enhanced biological phosphorus removal (S2EBPR) has been incorporated with B-stage process to enable simultaneous phosphorus and nitrogen removal. However, the dominating phosphorus accumulating organisms (PAOs) in this novel configuration has not been evaluated. The dominance of Acinetobacter was confirmed by 16S sequencing. In addition, single cell Raman spectrum (SCRS) analysis in couple with in situ fluorescence in situ hybridization (FISH) was applied to obtain the feature spectrum and verify the phosphorus release/uptake activity of Acinetobacter spp. The phenotypic profiling further suggested the dominance of Acinetobacter-like organisms among all poly-phosphorus containing organisms and only certain phenotypic Acinetobacter (oligotype 1) contribution to P-removal in a unique HRAS-P(D)N-S2EBPR system. The findings suggest that Acinetobacter may outcompete other heterotrophic organisms in EBPR systems due to their sensitivity to operational conditions. However, stable P-removal was only observed during a specific section of the operation period, coinciding with an increase in the VFA/P ratio. Further research is needed to identify the phenotypes of Acinetobacter responsible for P-removal in EBPR systems. The study contributes to a better understanding of the microbial ecology and engineering aspects of EBPR systems and wastewater treatment in general.

bioengineering↗

Comammox and Unknown Candidate AOBs Contribute to Nitrite Accumulation in An Integrated A-B stage process that Incorporates Side-stream EBPR (S2EBPR)

A novel integrated pilot-scale A-stage high rate activated sludge, B-stage short-cut biological nitrogen removal and side-stream enhanced biological phosphorus removal (A/B-shortcut N- S2EBPR) process for treating municipal wastewater was demonstrated with the aim to achieve simultaneous and carbon- and energy-efficient N and P removal. In this studied period, an average of 7.62 {+/-} 2.17 mg-N/L nitrite accumulation was achieved through atypical partial nitrification without canonical known NOB out-selection. Network analysis confirms the central hub of microbial community as Nitrospira, which was one to two orders of magnitude higher than canonical aerobic oxidizing bacteria (AOB) in a B-stage nitrification tank. The contribution of comammox Nitrospira as AOB was evidenced by the increased amoB/nxr ratio and higher ammonia oxidation activity. Furthermore, oligotyping analysis of Nitrospira revealed two dominant sub-clusters (microdiveristy) within the Nitrospira. The relative abundance of oligotype II, which is phylogenetically close to Nitrospira_midas_s_31566, exhibited a positive correlation with nitrite accumulation in the same operational period, suggesting its role as comammox Nitrospira. Additionally, the phylogenetic investigation suggested that heterotrophic organisms from the family Comamonadacea and the order Rhodocyclaceae embedding ammonia monooxygenase and hydroxylamine oxidase may function as heterotrophic nitrifiers. This is the first study that elucidated the impact of integrating the S2EBPR on nitrifying populations with implications on short-cut N removal. The unique conditions in the side-stream reactor, such as low ORP, favorable VFA concentrations and composition, seemed to exert different selective forces on nitrifying populations from those in conventional biological nutrient removal processes. The results provide new insights for integrating EBPR with short-cut N removal process for mainstream wastewater treatment.

bioengineering↗

The role of size in biostability of DNA tetrahedra

The potential for using DNA nanostructures for drug delivery applications requires understanding and ideally tuning their biostability. Here we investigate how biological degradation varies with size of a DNA nanostructure. We designed DNA tetrahedra of three edge lengths ranging from 13 to 20 bp and analyzed nuclease resistance for two nucleases and biostability in fetal bovine serum. We found that DNase I had similar digestion rates across sizes but appeared to incompletely digest the smallest tetrahedron, while T5 exonuclease was notably slower to digest the largest tetrahedron. In fetal bovine serum, the 20 bp tetrahedron was degraded ~four times faster than the 13 bp. These results show that DNA nanostructure size can influence nuclease degradation, but suggest a complex relationship that is nuclease specific.

synthetic biology↗

Proteome allocation is linked to transcriptional regulation through a modularized transcriptome

It has proved challenging to quantitatively relate the proteome to the transcriptome on a per-gene basis. Recent advances in data analytics have enabled a biologically meaningful modularization of the bacterial transcriptome. We thus investigated whether matched datasets of transcriptomes and proteomes from bacteria under diverse conditions could be modularized in the same way to reveal novel relationships between their compositions. We found that; 1) the modules of the proteome and the transcriptome are comprised of a similar list of gene products, 2) the modules in the proteome often represent combinations of modules from the transcriptome, 3) known transcriptional and post-translational regulation is reflected in differences between two sets of modules, allowing for knowledge-mapping when interpreting module functions, and 4) through statistical modeling, absolute proteome allocation can be inferred from the transcriptome alone. Quantitative and knowledge-based relationships can thus be found at the genome-scale between the proteome and transcriptome in bacteria.

bioengineering↗

Chronic industrial perturbation and seasonal change induces shift in the bacterial community from gammaproteobacteria to betaproteobacteria at Amlakhadi canal

Escalating proportions of industrially contaminated sites are one of the major catastrophes faced at the present time due to the industrial revolution. In the outlook of the obstacles associated with culturing the microbes, the direct metagenomic analysis of various complex niches is rapidly gaining attention. In this study, metagenomic approach using next generation sequencing technologies was applied to exemplify the taxonomic abundance and metabolic potential of the microbial community residing in Amlakhadi canal, Ankleshwar at two different seasons. All the metagenomes revealed a predominance of Proteobacteria phylum. However, difference was observed within class level where Gammaproteobacteria was relatively high in polluted metagenome in Summer while in Monsoon the abundance shifted to Betaproteobacteria. Similarly, significant statistical differences were obtained while comparing the genera amongst contaminated sites where Serratia, Achromobacter, Stenotrophomonas and Pseudomonas were abundant at one season and the dominance changed to Thiobacillus, Thauera, Acidovorax, Nitrosomonas, Sulfuricurvum, Novosphingobium, Hyphomonas and Geobacter at the next season. Further upon functional characterization, the microbiomes demonstrated diverse survival mechanisms adapted by the inherent microbial community such as degradation of aromatic compounds, heavy metal resistance, oxidative stress responses and multidrug resistance efflux pumps. The results have important implications in understanding and predicting the impacts of human-induced activities on microbial communities inhabiting natural niche and their responses in coping with the fluctuating pollution load.

microbiology↗

Immune response modulation by Pseudomonas aeruginosa persister cells

Bacterial persister cells - a metabolically dormant subpopulation tolerant to antimicrobials - contribute to chronic infections and are thought to evade host immunity. In this work, we studied the ability of Pseudomonas aeruginosa persister cells to withstand host innate immunity. We found that persister cells resist MAC-mediated killing by the complement system despite being bound by complement protein C3b at levels similar to regular vegetative cells, in part due to reduced bound C5b - and are engulfed at a lower rate (10-100 fold), even following opsonization. Once engulfed, persister cells resist killing and, contrary to regular vegetative cells which induce a M1 favored (CD80+/CD86+/CD206-, high levels of CXCL-8, IL-6, and TNF-) macrophage polarization, they initially induce a M2 favored macrophage polarization (CD80+/CD86+/CD206+, high levels of IL-10, and intermediate levels of CXCL-8, IL-6, and TNF-), which is skewed towards M1 favored polarization (high levels of CXCL-8 and IL-6, lower levels of IL-10) by 24 hours of infection, once persister cells awaken. Overall, our findings further establish the ability of persister cells to evade the innate host response and to contribute chronic infections.

microbiology↗