Medini K Annavajhala

• PhD in Environmental Engineering
• PostDoc Position at Columbia University

The Enterobacter cloacae complex (ECC) includes common nosocomial pathogens capable of producing a wide variety of infections. Broad-spectrum antibiotic resistance, including the recent emergence of resistance to last-resort carbapenems, has led to increased interest in this group of organisms and carbapenem-resistant E. cloacae complex (CREC) in p...

Infections by multidrug-resistant bacteria (MDRB) remain a leading cause of morbidity and mortality after liver transplantation (LT). Gut dysbiosis characteristic of end-stage liver disease may predispose patients to intestinal MDRB colonization and infection, in turn exacerbating dysbiosis. However, relationships between MDRB colonization and dysb...

A feedback loop between dysbiotic gut microbiota, increased translocation of microbial products such as lipopolysaccharide, and inflammation has been hypothesized to cause immune system dysfunction in early HIV infection. However, despite evidence of a chronic inflammatory phenotype in patients on antiretroviral therapy (ART), the role of oral micr...

Background Patients with COVID-19 may be at increased risk for secondary bacterial infections with MDR pathogens, including carbapenemase-producing Enterobacterales (CPE). Objectives We sought to rapidly investigate the clinical characteristics, population structure and mechanisms of resistance of CPE causing secondary infections in patients with...

Recent months have seen surges of SARS-CoV-2 infection across the globe with considerable viral evolution1–3. Extensive mutations in the spike protein may threaten the efficacy of vaccines and therapeutic monoclonal antibodies4. Two signature mutations of concern are E484K, which plays a crucial role in the loss of neutralizing activity of antibodi...

Background Extended-spectrum β-lactamase (ESBL)-producing Enterobacterales (ESBLE) are common pathogens in intensive care units (ICUs) causing infection at a range of body sites. While carbapenems are considered first-line agents, non-carbapenem beta-lactams such as piperacillin/tazobactam (TZP) and cefepime (FEP) are often used to treat non-severe...

Recurrent methicillin-susceptible Staphylococcus aureus colonization following successful decolonization in a neonatal intensive care unit (NICU) has been observed. Of 17 recolonization events, 53% were due to concordant strains; 19 different spa types were identified. Results of this study support sources of re-acquisition both intrinsic and extri...

Transmission of carbapenem-resistant Enterobacterales (CRE) in hospitals has been shown to occur through complex, multifarious networks driven by both clonal spread and horizontal transfer mediated by plasmids and other mobile genetic elements. We performed nanopore long-read sequencing on CRE isolates from a large urban hospital system to determin...

INTRODUCTION We examined the association of clinical, microbiological, and host response features of periodontitis with MRI markers of atrophy/cerebrovascular disease in the Washington Heights Inwood Columbia Aging Project (WHICAP) Ancillary Study of Oral Health. METHODS We analyzed 468 participants with clinical periodontal data, microbial plaque...

Background Infections caused by Enterobacterales resistant to third generation cephalosporins (Ceph-RE) are rising in incidence. Carbapenems are frequently used to treat Ceph-RE infections based largely on studies of patients with bacteremia. Data evaluating alternative antibiotic options in pneumonia are limited. We assessed outcomes in intensive...

Importance: Recent SARS-CoV-2 Omicron variant sublineages, including BA.4 and BA.5, may be associated with greater immune evasion and less protection against COVID-19 after vaccination. Objectives: To evaluate the estimated vaccine effectiveness (VE) of 2, 3, or 4 doses of COVID-19 mRNA vaccination among immunocompetent adults during a period of...

Nosocomial infections caused by multidrug-resistant (MDR) Enterobacter cloacae complex (ECC) pathogens are on the rise. However, the virulence strategies employed by these pathogens remain elusive. Here, we study the interaction of ECC clinical isolates with human serum to define how this pathogen evades the antimicrobial action of complement, one...

Background: Adults with cystic fibrosis (CF) are at increased risk for colon cancer. CF patients have reductions in intestinal bacteria that produce short chain fatty acids (SCFAs), although it is unclear whether this corresponds with intestinal SCFA levels and the presence of colonic neoplasia. The aim of this study was to compare gut microbiome...

Nirmatrelvir, an oral antiviral targeting the 3CL protease of SARS-CoV-2, has been demonstrated to be clinically useful against COVID-191,2. However, as SARS-CoV-2 has evolved to become resistant to other therapeutic modalities3-9, there is a concern that the same could occur for nirmatrelvir. Here, we have examined this possibility by in vitro pas...

Methicillin-susceptible Staphylococcus aureus (MSSA) is a more prevalent neonatal intensive care unit (NICU) pathogen than methicillin-resistant S. aureus (MRSA). However, the introduction and spread of MSSA, the role of systematic decolonization, and optimal infection prevention and control strategies remain incompletely understood. We previously...

Importance: Recent sublineages of the SARS–CoV–2 Omicron variant, including BA.4 and BA.5, may be associated with greater immune evasion and less protection against COVID–19 following vaccination. Objective: To evaluate the association between COVID–19 mRNA vaccination with 2, 3, or 4 doses among immunocompetent adults and the risk of medically att...

Liver transplant (LT) recipients have high rates of Clostridioides difficile infection (CDI), which has been associated with poor outcomes, including graft-related complications and mortality, in prior studies. Susceptibility to CDI is known to increase following perturbations in intestinal commensal bacteria that enable germination of C. difficile...

Background Many regions have experienced successive epidemic waves of COVID-19 since the emergence of SARS-CoV-2 with heterogeneous differences in mortality. Elucidating factors differentially associated with mortality between epidemic waves may inform clinical and public health strategies. Methods We examined clinical and demographic data among p...

Nirmatrelvir, an oral antiviral targeting the 3CL protease of SARS-CoV-2, has been demonstrated to be clinically useful in reducing hospitalization or death due to COVID-191,2. However, as SARS-CoV-2 has evolved to become resistant to other therapeutic modalities3-9, there is a concern that the same could occur for nirmatrelvir. Here, we have exami...

Mutations in the genome of SARS-CoV-2 can affect the performance of molecular diagnostic assays. In some cases, such as S-gene target failure, the impact can serve as a unique indicator of a particular SARS-CoV-2 variant and provide a method for rapid detection. Here, we describe partial ORF1ab gene target failure (pOGTF) on the cobas SARS-CoV-2 as...

Mutations in the genome of SARS-CoV-2 can affect the performance of molecular diagnostic assays. In some cases, such as S-gene target failure, the impact can serve as a unique indicator of a particular SARS-CoV-2 variant and provide a method for rapid detection. Here, we describe partial ORF1ab gene target failure (pOGTF) on the cobas SARS-CoV-2 as...

Background: SARS-CoV-2 antigen-based tests are well-calibrated to infectiousness and have a critical role to play in the COVID-19 public health response. We report the development and performance of a unique lateral flow immunoassay (LFA). Methods: Combinations of several monoclonal antibodies targeting multiple antigenic sites on the SARS-CoV-2...

Mutations in the viral genome of SARS-CoV-2 can impact the performance of molecular diagnostic assays. In some cases, such as S gene target failure, the impact can serve as a unique indicator of a particular SARS-CoV-2 variant and provide a method for rapid detection. Here we describe partial ORF1ab gene target failure (pOGTF) on the cobas® SARS-Co...

Background Carbapenem-resistant Enterobacterales (CRE) are highly concerning MDR pathogens. Horizontal transfer of broad-host-range IncN plasmids may contribute to the dissemination of the Klebsiella pneumoniae carbapenemase (KPC), spreading carbapenem resistance among unrelated bacteria. However, the population structure and genetic diversity of I...

K. pneumoniae sequence type 258 (Kp ST258) is a major cause of healthcare-associated pneumonia. However, it remains unclear how it causes protracted courses of infection in spite of its expression of immunostimulatory lipopolysaccharide, which should activate a brisk inflammatory response and bacterial clearance. We predicted that the metabolic str...

Many regions have experienced successive epidemic waves of COVID-19 since the emergence of SARS-CoV-2 with heterogeneous differences in mortality. Elucidating factors differentially associated with mortality between epidemic waves may inform clinical and public health strategies. We examined clinical and demographic data among patients admitted wit...

Bacterial-viral interactions in saliva have been associated with morbidity and mortality for respiratory viruses such as influenza and SARS-CoV. However, such transkingdom relationships during SARS-CoV-2 infection are currently unknown. Here, we aimed to elucidate the relationship between saliva microbiota and SARS-CoV-2 in a cohort of newly hospit...

Unlike immunocompetent hosts, the duration of viral persistence after infection with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) can be prolonged in immunosuppressed patients. Here, we present a case of viral persistence for over 19 weeks in a patient with a history of solid organ transplant and explore the clinical, virologic, and...

Background: Outbreaks of MRSA occur in NICUs and may be difficult to control. We describe an outbreak of mupirocin-resistant MRSA, molecular epidemiology of isolates and control. Methods: Medical record review of personnel contact with infants. MRSA isolates were analyzed by whole genome sequencing (WGS); single nucleotide polymorphisms (SNPs) w...

Background Staphylococcus aureus protein A (spa) typing can be used to expand characterization of the epidemiology of methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) in neonatal intensive care units (NICU). Methods From January 2017 to June 2018, twice-monthly surveillance for S. aureus was performed in an acade...

Recent months have seen surges of SARS-CoV-2 infection across the globe along with considerable viral evolution1–3. Extensive mutations in the spike protein may threaten efficacy of vaccines and therapeutic monoclonal antibodies4. Two signature mutations of concern are E484K, which plays a crucial role in the loss of neutralizing activity of antibo...

Recent months have seen surges of SARS-CoV-2 infection across the globe along with considerable viral evolution1–3. Extensive mutations in the spike protein may threaten efficacy of vaccines and therapeutic monoclonal antibodies4. Two signature mutations of concern are E484K, which plays a crucial role in the loss of neutralizing activity of antibo...

Klebsiella pneumoniae ST258 is a human pathogen associated with poor outcomes worldwide. We identify a member of the acyltransferase superfamily 3 (atf3), enriched within the ST258 clade, that provides a major competitive advantage for the proliferation of these organisms in vivo. Comparison of a wild-type ST258 strain (KP35) and a Δatf3 isogenic m...

Staphylococcus aureus is a prominent human pathogen that readily adapts to host immune defenses. Here, we show that, in contrast to Gram-negative pathogens, S. aureus induces a distinct airway immunometabolic response dominated by the release of the electrophilic metabolite, itaconate. The itaconate synthetic enzyme, IRG1, is activated by host mito...

Recent months have seen surges of SARS-CoV-2 infection across the globe along with considerable viral evolution. Extensive mutations in the spike protein of variants B.1.1.7, B1.351, and P.1 have raised concerns that the efficacy of current vaccines and therapeutic monoclonal antibodies could be threatened. In vitro studies have shown that one muta...

Purpose 3-indoxyl sulfate (3-IS) is an indole metabolism byproduct produced by commensal gut bacteria and excreted in the urine; low urinary 3-IS has been associated with increased mortality in bone marrow transplant recipients. This study investigated urinary 3-IS and patient outcomes in the ICU. Materials and methods Prospective study that colle...

Background The relationship between SARS-CoV-2 viral load and patient symptom duration in both in- and outpatients, and the impact of these factors on patient outcomes, are currently unknown. Understanding these associations is important to clinicians caring for patients with COVID-19. Methods We conducted an observational study between March 10–M...

Background Patients with COVID-19 may be at increased risk for secondary bacterial infections. At our quaternary care hospital in New York City, the rapid escalation of COVID-19 cases was accompanied by a massive surge in the need for hospital and critical care capacity. During this time, we noted a increase in infections caused by carbapenemase-pr...

Introduction: Although the microbiome is altered in various esophageal diseases, there is no direct evidence for a link between the oral or esophageal microbiome and underlying esophageal tissue. Here, we aimed to address these gaps through use of an antimicrobial mouth rinse to modify the esophageal microbiome and tissue gene expression. Methods...

Quantitative PCR (qPCR) is broadly used as the gold standard to quantify microbial community fractions in environmental microbiology and biotechnology. Benchmarking efforts to ensure the comparability of qPCR data for environmental bioprocesses are still scarce. Also, for partial nitritation/anammox (PN/A) systems systematic investigations are stil...

Polymyxin resistance (PR) threatens the treatment of carbapenem-resistant Klebsiella pneumoniae (CRKP) infections. PR frequently arises through chemical modification of the lipid A portion of lipopolysaccharide. Various mutations are implicated in PR, including in three two-component systems—CrrA/B, PmrA/B, and PhoP/Q—and the negative regulator Mgr...

Studies of the oxidative degradation of picric acid (2,4,6-trinitrophenol) by H2O2 catalyzed by a fluorine-tailed tetraamido macrocyclic ligand (TAML) activator of peroxides [FeIII{4,5-Cl2C6H2-1,2-(NCOCMe2NCO)2CF2}(OH2)]- (2) in neutral and mildly basic solutions revealed that oxidative degradation of this explosive demands components of phosphate...

The application of metagenomics and metatranscriptomics to field-scale engineered biological nitrogen removal (BNR) processes revealed a complex N-cycle network (the meta-azotome) therein in terms of microbial structure, potential and extant function. Autotrophic nitrification bore the imprint of well-documented Nitrosomonas and Nitrospira in most...

Background: There is a sparsity of data describing the periodontal microbiome in elderly individuals. We analyzed the association of subgingival bacterial profiles and clinical periodontal status in a cohort of participants in the Washington Heights-Inwood Columbia Aging Project (WHICAP). Methods: Dentate individuals underwent a full-mouth perio...

OBJECTIVES/GOALS: People living with HIV, despite antiretroviral therapy (ART), have increased burden of inflammatory and aging-related comorbidities such as periodontitis. Oral microbiota have been linked to periodontitis, but not in the context of HIV. We aim to compare relationships between the oral microbiome and periodontal disease in HIV+ vs...

Iron is essential for both microorganisms and their hosts. Although effects of dietary iron on gut microbiota have been described, the effect of systemic iron administration has yet to be explored. Here, we show that dietary iron, intravenous iron administration, and chronic transfusion in mice increase the availability of iron in the gut. These ir...

Background: Polymyxins are antimicrobials of last resort for the treatment of carbapenem-resistant Enterobacteriaceae, but resistance in 5% to >40% isolates has been reported. We conducted a genomic survey of clinical polymyxin-resistant (PR) Klebsiella pneumoniae to determine the molecular mechanisms of PR and the role of polymyxin exposure versu...

Mcr-1 , a plasmid-associated gene for colistin resistance, was first described in China in 2015 but its spread in the United States is unknown. We report detection of mcr-1- carrying E. coli ST117 in a cluster of three liver transplant recipients.

Rationale: Methicillin-resistant Staphylococcus aureus (MRSA) is a versatile human pathogen associated with diverse types of infections, ranging from benign colonization to sepsis. We postulated that MRSA must undergo specific genotypic and phenotypic changes to cause chronic pulmonary disease. Objectives: We investigated how MRSA adapts to the...

Metadata for selected isolates with publicly available whole-genome short-read data for phylogenetic analysis (Supplementary Figure S1).

Phylogenetic tree of representative E. cloacae complex (ECC) isolates showing relationships between Hoffmann clusters I-XII, genomic groups A-R, and selected sequence types (STs). At least one isolate with publicly available short-read sequences was selected from each ST previously reported in two recent genomic studies of CREC (Chavda et al., 2016...

Carbapenemase classes identified in carbapenem-resistant Enterobacter cloacae complex.

Carbapenemase alleles by reported location.

The molecular mechanisms of microbial adaptation to repeated anoxic–aerobic cycling were investigated by integrating whole community gene expression (metatranscriptomics) and physiological responses, including the production of nitric (NO) and nitrous (N2O) oxides. Anoxic–aerobic cycling was imposed for 17 days in a lab-scale full-nitrification mix...

Background Despite the global threat of CRE, data from resource-limited regions such as the Dominican Republic (DR) are limited. A lack of novel antibiotics and molecular diagnostic tools for outbreak detection, coupled with the role of travel in circulating CRE to and from the DR represent significant challenges to limiting their spread. Here, we...

Conventional biological nitrogen removal (BNR), comprised of nitrification and denitrification, is traditionally employed in wastewater treatment plants (WWTPs) to prevent eutrophication in receiving water bodies. More recently, the combination of selective ammonia to nitrite oxidation (nitritation) and autotrophic anaerobic ammonia oxidation (anam...

RPKM values indicating relative contributions of key microorganisms to potential production of enzymes involved in nitrogen metabolism.

Relevant carbon fixation pathways. cah, carbonic anhydrase; cdh, carbonic dehydratase; fdh, formate dehydrogenase; COdh, carbon monoxide dehydrogenase; acs, acetyl-CoA synthetase; cbbLS, RuBisCO; rlp, RuBisCO-like protein; acl, ATP citrate lyase; kgs, α-ketoglutarate synthase; frd, fumarate reductase.

BNR-capable organisms selected for targeted analysis.

Percent total aligned coding DNA sequences (CDS) in each biological nitrogen removal (BNR) process aligned to major genera involved in or related to BNR.

RPKM values indicating relative contributions of key microorganisms to potential production of enzymes involved in carbon metabolism.

Relevant nitrogen cycling pathways. Nrt, nitrate transporter; nxr/narGH, nitrite oxidoreductases; narK, nitrite/nitrate antiporter; foc/nirC, formate and nitrite transporter; nirS/nirK, nitrite reductase (cytochrome cd1-/iron-containing); nor, nitric oxide reductase; nos, nitrous oxide reductase; hdh/hzo, hydrazine dehydrogenase/hydrazine oxidoredu...

Treatment options for carbapenem-resistant Enterobacteriaceae (CRE) are limited. While Klebsiella pneumoniae harboring blaKPC account for most CRE, recent evidence points to increasing diversification of CRE. We determined whether CRE species and antibiotic resistance genotype influence response to relebactam (REL), a novel beta-lactamase inhibitor...

Purpose: Loss of colonization resistance within the gastrointestinal microbiome facilitates the expansion of pathogens and has been associated with death and infection in select populations. We tested whether gut microbiome features at the time of intensive care unit (ICU) admission predict death or infection. Methods: This was a prospective coh...

Recent reports have established the escalating threat of carbapenem-resistant Enterobacter cloacae complex (CREC). Here, we demonstrate that CREC has evolved as a highly antibiotic-resistant rather than highly virulent nosocomial pathogen. Applying genomics and Bayesian phylogenetic analyses to a 7-year collection of CREC isolates from a northern M...

Ceftazidime-avibactam (CAZ/AVI) is a promising novel treatment for carbapenem-resistant Enterobacteriaceae (CRE). Despite improved treatment outcomes compared to aminoglycoside- and colistin-based regimens, rapid evolution of CAZ/AVI resistance during treatment has previously been reported in Klebsiella pneumoniae ST258 blaKPC-3 harboring isolates....

Complete ammonia oxidation (comammox) to nitrate by certain Nitrospira-lineage bacteria (CMX) could contribute to overall nitrogen cycling in engineered biological nitrogen removal (BNR) processes in addition to the more well-documented nitrogen transformations by ammonia-oxidizing bacteria (AOB), nitrite-oxidizing bacteria (NOB), and anaerobic amm...

Reacting rationally: During the 1e oxidation of ferrocyanide by the catalytic TAML activator/H(2) O(2) , four Fe(IV) tetra-amido macrocyclic ligand (TAML) intermediates were detected that are involved in a fast acid-base equilibrium. The counterintuitive reactivity pattern is explained by the overall free-energy change during the reduction of Fe(IV...