Petros C Karakousis

Petros C Karakousis
Johns Hopkins Medicine | JHUSOM · School of Medicine

M.D.

About

209
Publications
28,903
Reads
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5,015
Citations
Additional affiliations
July 2018 - present
Johns Hopkins University School of Medicine
Position
  • Professor
Education
July 2002 - June 2005
Johns Hopkins Medicine
Field of study
  • Infectious Diseases
July 1998 - June 2001
Hospital of the University of Pennsylvania
Field of study
  • Internal Medicine
August 1994 - May 1998

Publications

Publications (209)
Article
Full-text available
Lengthy tuberculosis (TB) treatment is required to overcome the ability of a subpopulation of persistent Mycobacterium tuberculosis ( Mtb ) to remain in a non-replicating, antibiotic-tolerant state characterized by metabolic remodeling, including induction of the Rel Mtb -mediated stringent response. We developed a novel therapeutic DNA vaccine con...
Article
Full-text available
Background Host cell-membrane cholesterol, an important player in viral infections, is in constant interaction with serum high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C). Low serum lipid levels during hospital admission are associated with COVID-19 severity. However, the effect of antecedent serum lipid...
Article
Background: DNA vaccines fusing the chemokine MIP-3α (CCL20), which binds to CCR6 on immature dendritic cells (DCs), to melanoma-associated antigens have enhanced anti-tumor immunity and efficacy compared to vaccines lacking the chemokine. To further enhance the therapeutic effects of the vaccine, our laboratory has added type-I interferon (IFNα) a...
Preprint
Lengthy tuberculosis (TB) treatment is required to address the ability of a subpopulation of persistent Mycobacterium tuberculosis ( Mtb ) to remain in a non-replicating, antibiotic-tolerant state characterized by metabolic remodeling, including induction of the Rel Mtb -mediated stringent response. We developed a novel therapeutic DNA vaccine cons...
Article
Full-text available
Background Coronavirus disease 2019 (COVID-19) ranges from asymptomatic infection to severe illness. Cholesterol in the host cell plasma membrane plays an important role in the SARS-CoV-2 virus entry into cells. Serum lipids, especially low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), are in constant int...
Article
Full-text available
Objectives Pediatric tuberculosis (TB) remains difficult to diagnose. The plasma kynurenine to tryptophan ratio (K/T ratio) is a potential biomarker for TB diagnosis and treatment response but has not been assessed in children. Methods We performed a targeted diagnostic accuracy analysis of four biomarkers: kynurenine abundance, tryptophan abundan...
Article
Full-text available
Background Tuberculosis (TB) is one of the leading causes of death from a single infectious agent worldwide. The lengthy treatment regimen reflects the unique ability of a subpopulation of “persister” bacteria to remain in a nonreplicating state in the infected host through various adaptive strategies, including induction of the stringent response....
Article
To catalyze SARS-CoV-2 research including development of novel interventive and preventive strategies, we characterized progression of disease in depth in a robust COVID-19 animal model. In this model, male and female golden Syrian hamsters were inoculated intranasally with SARS-CoV-2 USA-WA1/2020. Groups of inoculated and mock-inoculated uninfecte...
Article
Full-text available
The stringent response is well conserved across bacterial species and is a key pathway involved both in bacterial survival and virulence and in the induction of antibiotic tolerance in Mycobacteria. It is mediated by the alarmone (p)ppGpp and the regulatory molecule inorganic polyphosphate in response to stress conditions such as nutrient starvatio...
Article
Full-text available
The Mycobacterium avium complex (MAC) is one of the most prevalent causes of nontuberculous mycobacteria pulmonary infection in the United States, and yet it remains understudied. Current MAC treatment requires more than a year of intermittent to daily combination antibiotic therapy, depending on disease severity. In order to shorten and simplify c...
Article
Full-text available
Background There is an urgent need for novel therapeutic strategies for reversing COVID-19-related lung inflammation. Recent evidence has demonstrated that the cholesterol-lowering agents, statins, are associated with reduced mortality in patients with various respiratory infections. We sought to investigate the relationship between statin use and...
Article
Full-text available
Objective: We sought to evaluate the utility of the GHS index in predicting the launch of COVID-19 vaccine rollout by OECD member countries. Methods: We collected country-level data on the preparedness to respond to infectious disease threats through vaccination rollout using the GHS index. OECD member countries were rank-ordered based on the pe...
Article
Full-text available
Tuberculosis (TB) and atherosclerotic cardiovascular disease (ASCVD) have a close epidemiological and pathogenetic overlap. Thus, it becomes essential to understand the relationship between ASCVD and TB outcomes. From our retrospective cohort on drug-susceptible TB patients at the National Taiwan University Hospital, we assessed the association of...
Article
Full-text available
Men experience more severe outcomes from coronavirus disease 2019 (COVID-19) than women. Golden Syrian hamsters were used to explore sex differences in the pathogenesis of a human clinical isolate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Preprint
Full-text available
To catalyze SARS-CoV-2 research including development of novel interventive and preventive strategies, we characterized progression of disease in depth in a robust COVID-19 animal model. In this model, male and female golden Syrian hamsters were inoculated intranasally with SARS-CoV-2 USA-WA1/2020. Groups of inoculated and mock-inoculated uninfecte...
Article
Full-text available
Background: Lipids play a central role in the pathogenesis of tuberculosis (TB). The effect of serum lipid levels on TB treatment (ATT) outcomes and their association with serum inflammatory markers have not yet been characterized. Methods: Our retrospective cohort study on drug-susceptible TB patients, at the National Taiwan University Hospital, a...
Article
Full-text available
Tuberculosis (TB) accounts for disproportionate morbidity and mortality among persons living with HIV (PLWH). Conventional methods of TB diagnosis, including smear microscopy and Xpert MTB/RIF, have lower sensitivity in PLWH. Novel high-throughput approaches, such as miRNAomics and metabolomics, may advance our ability to recognize subclinical and...
Article
Background: Although the incidence of tuberculosis (TB) is higher in males compared to females, the relationship of sex with TB treatment outcomes has not been adequately studied. Methods: We performed a retrospective cohort study and a systematic review and meta-analysis of observational studies during the last 10 years to assess sex difference...
Article
Full-text available
Tuberculosis (TB) is the leading cause of death from infection with a single bacterial pathogen. Host macrophages are the primary cell type infected with Mycobacterium tuberculosis ( Mtb ), the organism that causes TB. Macrophage response pathways are regulated by various factors, including microRNAs (miRNAs) and epigenetic changes that can shape t...
Article
Full-text available
COVID-19 is a novel disease caused by SARS-CoV-2. During the global vaccination rollout, it is vital to thoroughly understand the modes of transmission of the virus in order to prevent further spread of variants and ultimately to end the pandemic. The current literature suggests that SARS-CoV-2 is transmitted among the human population primarily th...
Preprint
Full-text available
Objective: Tuberculosis (TB) and atherosclerotic cardiovascular disease (ASCVD) have a close epidemiological and pathogenetic overlap. Thus, it becomes essential to understand the relationship between ASCVD and TB outcomes. Methods: From our retrospective cohort on drug-susceptible TB patients at the National Taiwan University Hospital, we assessed...
Preprint
Full-text available
Background Although the incidence of tuberculosis (TB) is higher in males compared to females, the relationship of sex with TB treatment outcomes has not been adequately studied. Methods We performed a retrospective cohort study and a systematic review and meta-analysis of observational studies during the last 10 years to assess the sex differences...
Preprint
Full-text available
In the ongoing coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), more severe outcomes are reported in males compared with females, including hospitalizations and deaths. Animal models can provide an opportunity to mechanistically interrogate causes of sex differences in the path...
Preprint
Full-text available
Mycobacterium avium complex (MAC) is one of the most prevalent causes of nontuberculous mycobacteria pulmonary infection in the United States, yet it remains understudied. Current MAC treatment requires more than a year of intermittent to daily combination antibiotic therapy, depending on disease severity. In order to shorten and simplify curative...
Article
Full-text available
Mycobacterium avium complex (MAC) is an increasingly important cause of morbidity and mortality, and is responsible for pulmonary infection in patients with underlying lung disease and disseminated disease in patients with AIDS. MAC has evolved various virulence strategies to subvert immune responses and persist in the infected host. Current treatm...
Chapter
Statins are a class of drugs that inhibit HMG-CoA reductase, the rate-limiting step in cholesterol biosynthesis, and are commonly used for primary and secondary prevention of cardiovascular disease. In addition to lowering cholesterol, statins also have broad immunomodulatory properties, and their use has been associated with improved clinical outc...
Book
This book discusses specific immune cell regulatory pathway(s), immune cell types, or other mechanisms involved in host responses to tuberculosis that can be potentially targeted for host-directed therapy (HDT). The pathways/mechanisms investigated are either protective – thus calling for pathway/factor enhancing drugs – or maladaptive – thus calli...
Article
Full-text available
Background Understanding the factors associated with disease severity and mortality in Coronavirus disease (COVID-19) is imperative to effectively triage patients. We performed a systematic review to determine the demographic, clinical, laboratory and radiological factors associated with severity and mortality in COVID-19. Methods We searched PubM...
Article
Full-text available
Pediatric tuberculosis (TB) remains a major global health problem. Improved pediatric diagnostics using readily available biosources are urgently needed. We used liquid chromatography-mass spectrometry to analyze plasma metabolite profiles of Indian children with active TB (n = 16) and age- and sex-matched, Mycobacterium tuberculosis-exposed but un...
Article
Full-text available
The ongoing COVID-19 pandemic has devastated many countries with ripple effects felt in various sectors of the global economy. In November 2019, the Global Health Security (GHS) Index was released as the first detailed assessment and benchmarking of 195 countries to prevent, detect, and respond to infectious disease threats. This paper presents the...
Article
Full-text available
Background Hypertension induces systemic inflammation, but its impact on the outcome of infectious diseases like tuberculosis (TB) is unknown. Calcium channel blockers (CCB) improve TB treatment outcomes in pre-clinical models, but their effect in patients with TB remain unclear. Methods This retrospective cohort study, including all patients > 18...
Article
Background: Mycobacterium tuberculosis (Mtb), the bacterium that causes tuberculosis (TB), causes 10 million infections and 1.5 million deaths per year worldwide. The success of Mtb as a human pathogen is directly related to its ability to suppress host responses, which are critical for clearing intracellular pathogens. Emerging evidence suggests...
Preprint
Full-text available
Background: Hypertension induces systemic inflammation, but its impact on the outcome of infectious diseases like tuberculosis (TB) is unknown. Calcium channel blockers (CCB) improve TB treatment outcomes in pre-clinical models, but their effect in patients with TB remain unclear. Methods: This retrospective cohort study, including all patients > 1...
Article
Full-text available
Mycobacterium avium complex (MAC) species are the most commonly isolated nontuberculous mycobacteria to cause pulmonary infections worldwide. The lengthy and complicated therapy required to cure lung disease due to MAC is at least in part due to the phenomenon of antibiotic tolerance. In this review, we will define antibiotic tolerance and contrast...
Article
Full-text available
The rise of drug-resistant tuberculosis (TB) poses a major risk to public health. Statins, which inhibit both cholesterol biosynthesis and protein prenylation branches of the mevalonate pathway, increase anti-tubercular antibiotic efficacy in animal models. However, the underlying molecular mechanisms are unknown. In this study, we used an in vitro...
Conference Paper
Background: The chemokine MIP-3α (CCL20) binds to CCR6 on immature dendritic cells (DCs). DNA vaccines fusing MIP-3α to melanoma-associated antigens gp100 and/or tyrosinase-related protein 2 (Trp2) have delayed tumor growth and increased survival time in the B16F10 mouse melanoma model system compared to vaccines lacking the chemokine. To further e...
Preprint
Full-text available
Background: Understanding the factors associated with disease severity and mortality in Coronavirus disease (COVID19) is imperative to effectively triage patients. We performed a systematic review to determine the demographic, clinical, laboratory and radiological factors associated with severity and mortality in COVID-19. Methods: We searched PubM...
Preprint
Full-text available
The ongoing COVID-19 pandemic has devastated many countries with ripple effects felt in various sectors of the global economy. In November 2019, the Global Health Security (GHS) Index was released as the first detailed assessment and benchmarking of 195 countries to prevent, detect, and respond to infectious disease threats. This paper presents the...
Article
Full-text available
A long duration of treatment and emerging drug resistance pose significant challenges for global tuberculosis (TB) eradication efforts. Therefore, there is an urgent need to develop novel strategies to shorten TB treatment regimens and to treat drug-resistant TB. Using an albumin-fusion strategy, we created a novel albumin-fused granulocyte-macroph...
Article
Full-text available
The lengthy and complicated current regimen required to treat drug-susceptible tuberculosis (TB) reflects the ability of Mycobacterium tuberculosis (Mtb) to persist in host tissues. The stringent response pathway, governed by the dual (p)ppGpp synthetase/hydrolase, Rel Mtb , is a major mechanism underlying Mtb persistence and antibiotic tolerance....
Article
Full-text available
Background The chemokine MIP-3α (CCL20) binds to CCR6 on immature dendritic cells. DNA vaccines fusing MIP-3α to melanoma-associated antigens have shown improved efficacy and immunogenicity in the B16F10 mouse melanoma model. Here, we report that the combination of type-I interferon therapy (IFNα) with 5-Aza-2′-deoxycitidine (5Aza) profoundly enhan...
Preprint
Statins, which inhibit both cholesterol biosynthesis and protein prenylation branches of the mevalonate pathway, increase anti-tubercular antibiotic efficacy in animal models. We investigated the mechanism of anti-tubercular action of simvastatin in Mycobacterium tuberculosis-infected human monocytic cells. We found that the anti-tubercular activit...
Article
Full-text available
Mycobacterium avium subsp. hominissuis (MAH) is increasingly recognized as a significant cause of morbidity, particularly in elderly patients or those with immune deficiency or underlying lung impairment. Disease due to MAH is particularly difficult to treat, often requiring years of antibiotic therapy. Identification of genes essential for MAH gro...
Article
Full-text available
The main advantage of animal models of infectious diseases over in vitro studies is the gain in understanding of the complex dynamics between the immune system and the pathogen. While small animal models have practical advantages over large animal models, it is crucial to be aware of their limitations. Although the small animal model at least needs...
Article
Background: Tuberculosis (TB) treatment is lengthy and complicated and patients often develop chronic lung disease. Recent attention has focused on host-directed therapies aimed at optimizing immune responses to M. tuberculosis (Mtb), as adjunctive treatment given with anti-tubercular drugs. In addition to their cholesterol-lowering properties, 3-...
Preprint
Full-text available
Mycobacterium avium (Mav) is increasingly recognized as a significant cause of morbidity, particularly in elderly patients or those with immune deficiency or underlying structural lung disease. Generally, Mav infection is treated with 2-3 antimicrobial drugs for at least 12 months. Identification of genes essential for Mav growth may yield novel st...
Preprint
The lengthy and complicated current regimen required to treat drug-susceptible tuberculosis (TB) reflects the ability of Mycobacterium tuberculosis (Mtb) to persist in host tissues. The stringent response pathway, governed by the dual (p)ppGpp synthetase/hydrolase, RelMtb, is a major mechanism underlying Mtb persistence and antibiotic tolerance. In...
Article
Full-text available
The stringent response enables Mycobacterium tuberculosis ( Mtb ) to shut down its replication and metabolism under various stresses. Here we show that Mtb lacking the stringent response enzyme Rel Mtb was unable to slow its replication rate during nutrient starvation. Metabolomics analysis revealed that the nutrient-starved rel Mtb -deficient stra...
Article
Full-text available
Infection with Mycobacterium avium is a significant cause of morbidity and its treatment requires the use of multiple antibiotics for more than 12 months. In the current work, we provide the genome sequence, gene annotations, gene ontology annotations, and protein homology data for M. avium strain 109 (MAC109), which has been used extensively in pr...
Article
Full-text available
Multidrug-resistant tuberculosis (TB), defined as TB resistant to the two first-line drugs, isoniazid and rifampin, is a serious challenge to global TB eradication efforts. Although mutations in rpoA or rpoC have been proposed to compensate for this fitness cost due to rpoB mutation in rifampicin-resistant Mycobacterium tuberculosis mutants, whethe...
Article
Full-text available
Mycobacterium tuberculosis is the etiologic agent of tuberculosis. The demand for new chemotherapeutics with unique mechanisms of action to treat (multi)resistant strains is an urgent need. The objective of this work was to test the effect of manganese(II) and copper(II) phenanthroline/dicarboxylate complexes against M. tuberculosis. The water-solu...