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Proceedings of the National Academy of Sciences

Tue, 09/19/2017 - 12:06
Campylobacter jejuni, a leading cause of bacterial gastroenteritis, is naturally competent. Like many competent organisms, C. jejuni restricts the DNA that can be used for transformation to minimize undesirable changes in the chromosome. Although C. jejuni can be transformed by C. jejuni-derived DNA, it is poorly transformed by the same...
Tue, 09/19/2017 - 12:06
Heavy metals from urban runoff preserved in sedimentary deposits record long-term economic and industrial development via the expansion and contraction of a city’s infrastructure. Lead concentrations and isotopic compositions measured in the sediments of the harbor of Ostia—Rome’s first harbor—show that lead pipes used in the water supply networks of...
Tue, 09/12/2017 - 16:40
The enteroinvasive bacterium Shigella is a facultative intracellular bacterium known, in vitro, to invade a large diversity of cells through the delivery of virulence effectors into the cell cytoplasm via a type III secretion system (T3SS). Here, we provide evidence that the injection of T3SS effectors does not necessarily result...
Tue, 09/12/2017 - 16:40
Genetic variant tied to risk of typhoid fever Salmonella bacteria. Image courtesy of Flickr/National Institute of Allergy and Infectious Diseases. Worldwide, Salmonella enterica serovar Typhi (S. Typhi) causes around 20 million typhoid infections every year, and 1–5% of infected individuals chronically carry the pathogen, notable among which is the storied...
Tue, 09/05/2017 - 12:50
Picornaviruses use internal ribosome entry sites (IRESs) to translate their genomes into protein. A typical feature of these IRESs is their ability to bind directly to the eukaryotic initiation factor (eIF) 4G component of the eIF4F cap-binding complex. Remarkably, the hepatitis A virus (HAV) IRES requires eIF4E for its translation,...
Tue, 08/29/2017 - 12:15
Cyclic di-3′,5′-adenosine monophosphate (c-di-AMP) is a broadly conserved bacterial second messenger that has been implicated in a wide range of cellular processes. Our earlier studies showed that c-di-AMP regulates central metabolism in Listeria monocytogenes by inhibiting its pyruvate carboxylase (LmPC), a biotin-dependent enzyme with biotin carboxylase (BC) and carboxyltransferase (CT)...
Tue, 07/11/2017 - 12:59
Trained in both human medical and veterinary sciences, Xiang-Jin Meng has made numerous contributions to the field of comparative viral pathogenesis. His achievements concerning emerging, reemerging, and zoonotic viral diseases include the discovery of swine and avian hepatitis E viruses (HEV) and the invention of a commercial vaccine against porcine...
Tue, 06/27/2017 - 14:09
Botulism is characterized by flaccid paralysis, which can be caused by intoxication with any of the seven known serotypes of botulinum neurotoxin (BoNT), all of which disrupt synaptic transmission by endoproteolytic cleavage of SNARE proteins. BoNT serotype A (BoNT/A) has the most prolonged or persistent effects, which can last several...
Tue, 06/20/2017 - 12:04
The Picornaviridae are a diverse family of RNA viruses including many pathogens of medical and veterinary importance. Classically considered “nonenveloped,” recent studies show that some picornaviruses, notably hepatitis A virus (HAV; genus Hepatovirus) and some members of the Enterovirus genus, are released from cells nonlytically in membranous vesicles. To better...
Tue, 06/13/2017 - 12:29
Listeria monocytogenes is a common food-borne pathogen that can disseminate from the intestine and infect multiple organs. Here, we used sequence tag-based analysis of microbial populations (STAMP) to investigate L. monocytogenes population dynamics during infection. We created a genetically barcoded library of murinized L. monocytogenes and then used deep sequencing...
Tue, 05/30/2017 - 12:39
XIAP-associated factor 1 (XAF1) is a tumor suppressor that is commonly inactivated in multiple human neoplasms. However, the molecular mechanism underlying its proapoptotic function remains largely undefined. Here, we report that XAF1 induction by heavy metals triggers an apoptotic switch of stress response by destabilizing metallothionein 2A (MT2A). XAF1 directly...
Tue, 04/18/2017 - 12:47
Global distribution of hepatocellular carcinomas (HCCs) is dominated by its incidence in developing countries, accounting for >700,000 estimated deaths per year, with dietary exposures to aflatoxin (AFB1) and subsequent DNA adduct formation being a significant driver. Genetic variants that increase individual susceptibility to AFB1-induced HCCs are poorly understood. Herein, it...
Tue, 04/11/2017 - 13:39
Aflatoxin B1 (AFB1) and/or hepatitis B and C viruses are risk factors for human hepatocellular carcinoma (HCC). Available evidence supports the interpretation that formation of AFB1-DNA adducts in hepatocytes seeds a population of mutations, mainly G:C→T:A, and viral processes synergize to accelerate tumorigenesis, perhaps via inflammation. Responding to a need...
Tue, 02/28/2017 - 11:40
The toxigenic classical and El Tor biotype Vibrio cholerae serogroup O1 strains are generated by lysogenization of host-type–specific cholera toxin phages (CTX phages). Experimental evidence of the replication and transmission of an El Tor biotype-specific CTX phage, CTX-1, has explained the evolution of V. cholerae El Tor biotype strains. The...
Tue, 01/24/2017 - 12:24
Hepatitis A virus (HAV) infects ∼1.4 million people annually and, although there is a vaccine, there are no licensed therapeutic drugs. HAV is unusually stable (making disinfection problematic) and little is known of how it enters cells and releases its RNA. Here we report a potent HAV-specific monoclonal antibody, R10,...
Tue, 01/17/2017 - 15:48
CELL BIOLOGY Correction for “DNA polymerase ζ limits chromosomal damage and promotes cell survival following aflatoxin exposure,” by Ying-Chih Lin, Nichole Owen, Irina G. Minko, Sabine S. Lange, Liang Li, Michael P. Stone, Richard D. Wood, Amanda K. McCullough, and R. Stephen Lloyd, which appeared in issue 48, November 29,...
Tue, 01/10/2017 - 13:16
Domoic acid is a potent neurotoxin produced by certain marine microalgae that can accumulate in the foodweb, posing a health threat to human seafood consumers and wildlife in coastal regions worldwide. Evidence of climatic regulation of domoic acid in shellfish over the past 20 y in the Northern California Current...
Tue, 12/27/2016 - 13:37
In Salmonella enterica serovar Typhimurium, Mg2+ limitation induces transcription of the mgtA Mg2+ transport gene, but the mechanism involved is unclear. The 5′ leader of the mgtA mRNA contains a 17-codon, proline-rich ORF, mgtL, whose translation regulates the transcription of mgtA [Park S-Y et al. (2010) Cell 142:737–748]. Rapid translation...
Tue, 12/20/2016 - 13:10
Infection by the human bacterial pathogen Listeria monocytogenes is mainly controlled by the positive regulatory factor A (PrfA), a member of the Crp/Fnr family of transcriptional activators. Published data suggest that PrfA requires the binding of a cofactor for full activity, and it was recently proposed that glutathione (GSH) could...
Tue, 12/06/2016 - 12:51
The study of the isotopic fractionation of endogen elements and toxic heavy metals in living organisms for biomedical applications, and for metabolic and toxicological studies, is a cutting-edge research topic. This paper shows that human neuroblastoma cells incorporated small amounts of uranium (U) after exposure to 10 µM natural U,...
Tue, 11/29/2016 - 11:48
Vibrio cholerae has caused seven cholera pandemics since 1817, imposing terror on much of the world, but bacterial strains are currently only available for the sixth and seventh pandemics. The El Tor biotype seventh pandemic began in 1961 in Indonesia, but did not originate directly from the classical biotype sixth-pandemic...
Tue, 11/29/2016 - 11:48
Routine dietary consumption of foods that contain aflatoxins is the second leading cause of environmental carcinogenesis worldwide. Aflatoxin-driven mutagenesis is initiated through metabolic activation of aflatoxin B1 (AFB1) to its epoxide form that reacts with N7 guanine in DNA. The resulting AFB1-N7-dG adduct undergoes either spontaneous depurination or imidazole-ring opening...
Tue, 10/25/2016 - 13:24
All of the heme-degrading enzymes that have been characterized to date require molecular oxygen as a cosubstrate. Escherichia coli O157:H7 has been shown to express heme uptake and transport proteins, as well as use heme as an iron source. This enteric pathogen colonizes the anaerobic space of the lower intestine...
Tue, 10/18/2016 - 12:32
The rise of inorganic–biological hybrid organisms for solar-to-chemical production has spurred mechanistic investigations into the dynamics of the biotic–abiotic interface to drive the development of next-generation systems. The model system, Moorella thermoacetica–cadmium sulfide (CdS), combines an inorganic semiconductor nanoparticle light harvester with an acetogenic bacterium to drive the...
Tue, 10/04/2016 - 13:10
Sequence analyses of pathogen genomes facilitate the tracking of disease outbreaks and allow relationships between strains to be reconstructed and virulence factors to be identified. However, these methods are generally used after an outbreak has happened. Here, we show that support vector machine analysis of bovine E. coli O157 isolate...
Tue, 09/20/2016 - 11:46
Infections due to clonal expansion of highly virulent bacterial strains are clear and present threats to human and animal health. Association of genetic changes with disease is now a routine, but identification of causative mutations that enable disease remains difficult. Campylobacter jejuni is an important zoonotic pathogen transmitted to humans...
Tue, 09/06/2016 - 12:56
Cells migrate by directing Ras-related C3 botulinum toxin substrate 1 (Rac1) and cell division control protein 42 (Cdc42) activities and by polymerizing actin toward the leading edge of the cell. Previous studies have proposed that this polarization process requires a local positive feedback in the leading edge involving Rac small...
Tue, 07/26/2016 - 13:56
Memory γδ T cells are important for the clearance of Listeria monocytogenes infection in the intestinal mucosa. However, the mechanisms by which memory γδ T cells provide protection against secondary oral infection are poorly understood. Here we used a recombinant strain of L. monocytogenes that efficiently invades the intestinal epithelium...
Tue, 07/12/2016 - 14:10
It is estimated that ∼2.7 million tons poly(carbonate)s (PCs) are produced annually worldwide. In 2008, retailers pulled products from store shelves after reports of bisphenol A (BPA) leaching from baby bottles, reusable drink bottles, and other retail products. Since PCs are not typically recycled, a need for the repurposing of...
Tue, 06/28/2016 - 13:02
RNA structures are fundamentally important for RNA function. Dynamic, condition-dependent structural changes are able to modulate gene expression as shown for riboswitches and RNA thermometers. By parallel analysis of RNA structures, we mapped the RNA structurome of Yersinia pseudotuberculosis at three different temperatures. This human pathogen is exquisitely responsive to...
Tue, 06/14/2016 - 13:48
Polysaccharide capsules are surface structures that are critical for the virulence of many Gram-negative pathogenic bacteria. Salmonella enterica serovar Typhi is the etiological agent of typhoid fever. It produces a capsular polysaccharide known as “Vi antigen,” which is composed of nonstoichiometrically O-acetylated α-1,4-linked N-acetylgalactosaminuronic acid residues. This glycan is a...
Tue, 06/07/2016 - 12:33
The Q fever bacterium Coxiella burnetii replicates inside host cells within a large Coxiella-containing vacuole (CCV) whose biogenesis relies on the Dot/Icm-dependent secretion of bacterial effectors. Several membrane trafficking pathways contribute membranes, proteins, and lipids for CCV biogenesis. These include the endocytic and autophagy pathways, which are characterized by...
Tue, 05/31/2016 - 12:27
Vibrio parahaemolyticus is the most common cause of seafood-borne gastroenteritis worldwide and a blight on global aquaculture. This organism requires a horizontally acquired type III secretion system (T3SS2) to infect the small intestine, but knowledge of additional factors that underlie V. parahaemolyticus pathogenicity is limited. We used transposon-insertion sequencing to...
Tue, 05/24/2016 - 12:13
To acquire essential Fe(III), bacteria produce and secrete siderophores with high affinity and selectivity for Fe(III) to mediate its uptake into the cell. Here, we show that the periplasmic binding protein CeuE of Campylobacter jejuni, which was previously thought to bind the Fe(III) complex of the hexadentate siderophore enterobactin (Kd...
Tue, 05/17/2016 - 12:47
Listeria monocytogenes is responsible for gastroenteritis in healthy individuals and for a severe invasive disease in immunocompromised patients. Among the three identified L. monocytogenes evolutionary lineages, lineage I strains are overrepresented in epidemic listeriosis outbreaks, but the mechanisms underlying the higher virulence potential of strains of this lineage remain elusive....
Tue, 04/26/2016 - 13:02
Upon entry into host cells, intracellular bacterial pathogens establish a variety of replicative niches. Although some remodel phagosomes, others rapidly escape into the cytosol of infected cells. Little is currently known regarding how professional intracytoplasmic pathogens, including Shigella, mediate phagosomal escape. Shigella, like many other Gram-negative bacterial pathogens, uses a...
Tue, 03/29/2016 - 12:15
Although it is known that diverse bacterial flagellar motors produce different torques, the mechanism underlying torque variation is unknown. To understand this difference better, we combined genetic analyses with electron cryo-tomography subtomogram averaging to determine in situ structures of flagellar motors that produce different torques, from Campylobacter and Vibrio species....
Tue, 03/08/2016 - 13:49
Common environmental contaminants such as bisphenols and phthalates and persistent contaminants such as polychlorinated biphenyls are thought to influence tissue homeostasis and carcinogenesis by acting as disrupters of endocrine function. In this study we investigated the direct effects of exposure to bisphenol A (BPA), mono-n-butyl phthalate (Pht), and polychlorinated biphenyl...
Tue, 01/19/2016 - 14:53
Necrotizing fasciitis (NF) caused by flesh-eating bacteria is associated with high case fatality. In an earlier study, we reported infection of an immunocompetent individual with multiple strains of Aeromonas hydrophila (NF1–NF4), the latter three constituted a clonal group whereas NF1 was phylogenetically distinct. To understand the complex interactions of these...
Tue, 01/12/2016 - 12:07
Pigs are important intermediate hosts for generating novel influenza viruses. The Eurasian avian-like H1N1 (EAH1N1) swine influenza viruses (SIVs) have circulated in pigs since 1979, and human cases associated with EAH1N1 SIVs have been reported in several countries. However, the biologic properties of EAH1N1 SIVs are largely unknown. Here, we...
Tue, 12/22/2015 - 19:58
Pain management would be greatly enhanced by a formulation that would provide local anesthesia at the time desired by patients and with the desired intensity and duration. To this end, we have developed near-infrared (NIR) light-triggered liposomes to provide on-demand adjustable local anesthesia. The liposomes contained tetrodotoxin (TTX), which has...
Tue, 12/08/2015 - 13:14
Hepatitis A virus (HAV) is an ancient and ubiquitous human pathogen recovered previously only from primates. The sole species of the genus Hepatovirus, existing in both enveloped and nonenveloped forms, and with a capsid structure intermediate between that of insect viruses and mammalian picornaviruses, HAV is enigmatic in its origins....
Tue, 12/08/2015 - 13:14
The History of HAV Earliest descriptions of epidemic liver disease, most likely due to hepatitis A virus (HAV), can be found in ancient Chinese literature, and similar observations, often in association with conflict and social disruption, have appeared on many occasions. However, evidence that the infection was of viral etiology...
Tue, 10/06/2015 - 12:03
Enterohemorrhagic Escherichia coli (EHEC) is one of the leading causes of bacterial enteric infections worldwide, causing ∼100,000 illnesses, 3,000 hospitalizations, and 90 deaths annually in the United States alone. These illnesses have been linked to consumption of contaminated animal products and vegetables. Currently, other than thermal inactivation, there are no...
Tue, 10/06/2015 - 12:03
Food safety is a critical issue worldwide, and responsibility for ensuring and enhancing safety in the food chain is collectively shared by all involved, from producers to preparation to food service. Just over a century ago, the issues of food safety and production were brought to the forefront of public...
Wed, 09/30/2015 - 03:20
MICROBIOLOGY Correction for “The opportunistic marine pathogen Vibrio parahaemolyticus becomes virulent by acquiring a plasmid that expresses a deadly toxin,” by Chung-Te Lee, I-Tung Chen, Yi-Ting Yang, Tzu-Ping Ko, Yun-Tzu Huang, Jiun-Yan Huang, Ming-Fen Huang, Shin-Jen Lin, Chien-Yu Chen, Shih-Shuen Lin, Donald V. Lightner, Han-Ching Wang, Andrew H.-J. Wang, Hao-Ching...
Wed, 09/30/2015 - 03:20
Methylmercury (MeHg) is a potent neurotoxin that is biomagnified approximately 1–10 million-fold in aquatic carnivores such as the Northern elephant seal (Mirounga angustirostris), whose excreta and molted pelage, in turn, constitute a source of environmental MeHg contamination at the base of marine food chains. The potential for this top-down contamination...
Wed, 09/30/2015 - 03:20
Mercury and marine mammals Northern elephant seals accumulate MeHg from their prey in the North Pacific. Image courtesy of James Harvey (Moss Landing Marine Laboratories, Moss Landing, CA). Methylmercury (MeHg) is a neurotoxin that accumulates in marine food chains, posing a threat to environmental and human health. High Hg concentrations...
Wed, 09/23/2015 - 03:20
Elevated levels of neurotoxic methylmercury in Arctic food-webs pose health risks for indigenous populations that consume large quantities of marine mammals and fish. Estuaries provide critical hunting and fishing territory for these populations, and, until recently, benthic sediment was thought to be the main methylmercury source for coastal fish. New...
Thu, 09/03/2015 - 03:20
In 2006, a deadly Escherichia coli O157:H7 outbreak in bagged spinach was traced to California’s Central Coast region, where >70% of the salad vegetables sold in the United States are produced. Although no definitive cause for the outbreak could be determined, wildlife was implicated as a disease vector. Growers were...

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