Background: Microbe-microbe and host-microbe interactions in a microbiome play a vital role in bo... more Background: Microbe-microbe and host-microbe interactions in a microbiome play a vital role in both health and disease. However, the structure of the microbial community and the colonization patterns are highly complex to infer even under controlled wet laboratory conditions. In this study, we investigate what information, if any, can be provided by a Bayesian Network (BN) about a microbial community. Unlike the previously proposed Co-occurrence Networks (CoNs), BNs are based on conditional dependencies and can help in revealing complex associations. Results: In this paper, we propose a way of combining a BN and a CoN to construct a signed Bayesian Network (sBN). We report a surprising association between directed edges in signed BNs and known colonization orders. Conclusions: BNs are powerful tools for community analysis and extracting influences and colonization patterns, even though the analysis only uses an abundance matrix with no temporal information. We conclude that directed...
Angewandte Chemie (International ed. in English), Jun 25, 2016
Muropeptides are a group of bacterial natural products generated from the cell wall in the course... more Muropeptides are a group of bacterial natural products generated from the cell wall in the course of its turnover. These compounds are cell-wall recycling intermediates and are also involved in signaling within the bacterium. However, the identity of these signaling molecules remains elusive. The identification and characterization of 20 muropeptides from Pseudomonas aeruginosa is described. The least abundant of these metabolites is present at 100 and the most abundant at 55,000 molecules per bacterium. Analysis of these muropeptides under conditions of induction of resistance to a β-lactam antibiotic identified two signaling muropeptides (N-acetylglucosamine-1,6-anhydro-N-acetylmuramyl pentapeptide and 1,6-anhydro-N-acetylmuramyl pentapeptide). Authentic synthetic samples of these metabolites were shown to activate expression of β-lactamase in the absence of any β-lactam antibiotic, thus indicating that they serve as chemical signals in this complex biochemical pathway.
Background: Communicating about antimicrobial resistance (AMR) to the public is challenging. Me... more Background: Communicating about antimicrobial resistance (AMR) to the public is challenging. Methods: We developed a dictionary of terms commonly used to communicate about AMR. For each term, we developed learning points to explain AMR and related concepts in plain language. We conducted a pilot evaluation in 374 high school students in Ubon Ratchathani, Thailand. In three 50-minute sessions, students were asked to answer five true/false questions using a paper-based questionnaire. The first session assessed their understanding of AMR at baseline, the second after searching the internet, and the third after the provision of the printed AMR dictionary and its web address. Results: We developed the AMR dictionary as a web-based application (www.amrdictionary.net). The Thai version of the AMR dictionary included 35 terms and associated learning points, seven figures displaying posters promoting AMR awareness in Thailand, and 66 recommended online videos. In the pretest, the propo...
Extracellular polymeric substances (EPS) have major impact on biofouling of reverse osmosis (RO) ... more Extracellular polymeric substances (EPS) have major impact on biofouling of reverse osmosis (RO) membranes. On one hand, EPS can reduce membrane permeability and on the other, EPS production by the primary colonizers may influence their deposition and attachment rate and subsequently affect the biofouling propensity of the membrane. The role of bacterial exopolysaccharides in bacterial deposition followed by the biofouling potential of an RO membrane was evaluated using an alginate overproducing (mucoid) Pseudomonas aeruginosa. The mucoid P. aeruginosa PAOmucA22 was compared with its isogenic nonmucoid prototypic parent PAO1 microscopically in a radial stagnation point flow (RSPF) system for their bacterial deposition characteristics. Then, biofouling potential of PAO1 and PAOmucA22 was determined in a crossflow rectangular plate-and-frame membrane cell, in which the strains were cultivated on a thin-film composite, polyamide, flat RO membrane coupon (LFC-1) under laminar flow conditions. In the RSPF system, the observed deposition rate of the mucoid strain was between 5- and 10-fold lower than of the wild type using either synthetic wastewater medium (with ionic strength of 14.7 mM and pH 7.4) or 15 mM KCl solution (pH of 6.2). The slower deposition rate of the mucoid strain is explained by 5- to 25-fold increased hydrophilicity of the mucoid strain as compared to the isogenic wild type, PAO1. Corroborating with these results, a significant delay in the onset of biofouling of the RO membrane was observed when the mucoid strain was used as the membrane colonizer, in which the observed time for the induced permeate flux decline was delayed (ca. 2-fold). In conclusion, the lower initial cell attachment of the mucoid strain decelerated biofouling of the RO membrane. Bacterial deposition and attachment is a critical step in biofilm formation and governed by intimate interactions between outer membrane proteins of the bacteria and the surface. Shielding these interactions by a hydrated and hydrophilic alginate capsule is shown to dramatically lessen the biofouling potential of the membrane colonizers.
Communications in Soil Science and Plant Analysis, 2014
Agricultural practices influence the community structure and functional diversity of soil microor... more Agricultural practices influence the community structure and functional diversity of soil microorganisms. In the present study, the impact of nutrient-management systems on the changes in the biological properties of Indian semi-arid Alfisol was assessed. The long-term organically managed (OGF) and inorganically fertilized (IGF) soils from century-old experimental plots were compared for eubacterial diversity using amplicon length heterogeneity PCR (LH-PCR) targeting three hypervariable domains (V1, V1_V2, and V3) of 16S rRNA gene. Of these domains, V1_V2 could discriminate the bacterial communities between the soil types. The relative ratios of amplicons differed between OGF and ICF soils, and eubacterial diversity was decreased substantially because of the inorganic chemical fertilizers, as compared to organic amendments. The Bray–Curtis similarity index and diversity indices of amplicons were greater in OGF soil than in ICF soil. This polyphasic approach revealed that the diversity and functionality of the soil eubacterial community were encouraged by long-term organic manures more than inorganic chemical fertilizers.
A unique nanoelectronic platform, based on single-walled carbon nanotubes (SWNTs), has been fabri... more A unique nanoelectronic platform, based on single-walled carbon nanotubes (SWNTs), has been fabricated for measuring electrical transport in single-molecule DNA. We have tested 80 base pairs of single- and double-stranded DNA (ssDNA and dsDNA, respectively) of complex base sequences. About a 25-40 pA current (at 1 V) was measured for the dsDNA molecule covalently attached to the SWNT electrode at its termini. In the absence of base pair stacking, a ssDNA carries a feeble current of approximately 1 pA or less. Gate-voltage-dependent I-V characteristics revealed that the bridging dsDNA molecule acts as a p-type channel between SWNT source and drain electrodes.
In this paper, we present a new approach that will facilitate the process of drawing meaningful c... more In this paper, we present a new approach that will facilitate the process of drawing meaningful conclusions that are likely to be useful to a biologist who may be interested in only a specific functional aspect of the organism (rather than the entire genome). This is achieved by constructing a comprehensive relational database and an intelligent, userfriendly query system. With the help of simple examples, we show how a biologist with no prior knowledge of databases can use this system. Our database can be queried from the URL: http://biorg.cs.fiu.edu/TFBM/
Pathogenicity of Pseudomonas aeruginosa, a major cause of many acute and chronic human infections... more Pathogenicity of Pseudomonas aeruginosa, a major cause of many acute and chronic human infections, is determined by tightly regulated expression of multiple virulence factors. Quorum sensing (QS) controls expression of many of these pathogenic determinants. Previous microarray studies have shown that the AmpC β-lactamase regulator AmpR, a member of the LysR family of transcription factors, also controls non-β-lactam resistance and multiple virulence mechanisms. Using RNA-Seq and complementary assays, this study further expands the AmpR regulon to include diverse processes such as oxidative stress, heat shock and iron uptake. Importantly, AmpR affects many of these phenotypes, in part, by regulating expression of non-coding RNAs such as rgP32, asRgsA, asPrrF1 and rgRsmZ. AmpR positively regulates expression of the major QS regulators LasR, RhlR and MvfR, and genes of the Pseudomonas quinolone system. Chromatin immunoprecipitation (ChIP)-Seq and ChIP–quantitative real-time polymerase ...
Causal inference in biomedical research allows us to shift the paradigm from investigating associ... more Causal inference in biomedical research allows us to shift the paradigm from investigating associational relationships to causal ones. Inferring causal relationships can help in understanding the inner workings of biological processes. Association patterns can be coincidental and may lead to wrong conclusions about causality in complex systems. Microbiomes are highly complex, diverse, and dynamic environments. Microbes are key players in human health and disease. Hence knowledge of critical causal relationships among the entities in a microbiome, and the impact of internal and external factors on microbial abundance and their interactions are essential for understanding disease mechanisms and making appropriate treatment recommendations. In this paper, we employ causal inference techniques to understand causal relationships between various entities in a microbiome, and to use the resulting causal network to make useful computations. We introduce a novel pipeline for microbiome analy...
Background Bacterial vaginosis (BV) increases the risk of many sexually transmitted infections. T... more Background Bacterial vaginosis (BV) increases the risk of many sexually transmitted infections. The co-occurrence of persistent BV and high-risk HPV (HrHPV) increases the risk of developing cervical cancer. This study aims to investigate the co-occurrence of HrHPV and BV among young women in the US. Methods Stored vaginal swabs were acquired from a previously completed clinical trial. The kinds of bacteria present in the samples were identified by classifying 16S rRNA gene sequences in each sample using high-throughput pyrosequencing. HPV genotyping was performed using quantitative polymerase chain reaction using TaqMan probes in a customized plate (ThermoFisher Scientific; Waltham, Massachusetts). BV was classified using Nugent Scores of Gram Stain. Results Eighty reproductive age African American (AA) women were included in the analysis. The point prevalence of HrHPV was 48.1% (95%CI: 37–59%). The mean age of the participants was 21.4 years (SD: 2.11), 81.2% graduated high school....
Background: Microbe-microbe and host-microbe interactions in a microbiome play a vital role in bo... more Background: Microbe-microbe and host-microbe interactions in a microbiome play a vital role in both health and disease. However, the structure of the microbial community and the colonization patterns are highly complex to infer even under controlled wet laboratory conditions. In this study, we investigate what information, if any, can be provided by a Bayesian Network (BN) about a microbial community. Unlike the previously proposed Co-occurrence Networks (CoNs), BNs are based on conditional dependencies and can help in revealing complex associations. Results: In this paper, we propose a way of combining a BN and a CoN to construct a signed Bayesian Network (sBN). We report a surprising association between directed edges in signed BNs and known colonization orders. Conclusions: BNs are powerful tools for community analysis and extracting influences and colonization patterns, even though the analysis only uses an abundance matrix with no temporal information. We conclude that directed...
Angewandte Chemie (International ed. in English), Jun 25, 2016
Muropeptides are a group of bacterial natural products generated from the cell wall in the course... more Muropeptides are a group of bacterial natural products generated from the cell wall in the course of its turnover. These compounds are cell-wall recycling intermediates and are also involved in signaling within the bacterium. However, the identity of these signaling molecules remains elusive. The identification and characterization of 20 muropeptides from Pseudomonas aeruginosa is described. The least abundant of these metabolites is present at 100 and the most abundant at 55,000 molecules per bacterium. Analysis of these muropeptides under conditions of induction of resistance to a β-lactam antibiotic identified two signaling muropeptides (N-acetylglucosamine-1,6-anhydro-N-acetylmuramyl pentapeptide and 1,6-anhydro-N-acetylmuramyl pentapeptide). Authentic synthetic samples of these metabolites were shown to activate expression of β-lactamase in the absence of any β-lactam antibiotic, thus indicating that they serve as chemical signals in this complex biochemical pathway.
Background: Communicating about antimicrobial resistance (AMR) to the public is challenging. Me... more Background: Communicating about antimicrobial resistance (AMR) to the public is challenging. Methods: We developed a dictionary of terms commonly used to communicate about AMR. For each term, we developed learning points to explain AMR and related concepts in plain language. We conducted a pilot evaluation in 374 high school students in Ubon Ratchathani, Thailand. In three 50-minute sessions, students were asked to answer five true/false questions using a paper-based questionnaire. The first session assessed their understanding of AMR at baseline, the second after searching the internet, and the third after the provision of the printed AMR dictionary and its web address. Results: We developed the AMR dictionary as a web-based application (www.amrdictionary.net). The Thai version of the AMR dictionary included 35 terms and associated learning points, seven figures displaying posters promoting AMR awareness in Thailand, and 66 recommended online videos. In the pretest, the propo...
Extracellular polymeric substances (EPS) have major impact on biofouling of reverse osmosis (RO) ... more Extracellular polymeric substances (EPS) have major impact on biofouling of reverse osmosis (RO) membranes. On one hand, EPS can reduce membrane permeability and on the other, EPS production by the primary colonizers may influence their deposition and attachment rate and subsequently affect the biofouling propensity of the membrane. The role of bacterial exopolysaccharides in bacterial deposition followed by the biofouling potential of an RO membrane was evaluated using an alginate overproducing (mucoid) Pseudomonas aeruginosa. The mucoid P. aeruginosa PAOmucA22 was compared with its isogenic nonmucoid prototypic parent PAO1 microscopically in a radial stagnation point flow (RSPF) system for their bacterial deposition characteristics. Then, biofouling potential of PAO1 and PAOmucA22 was determined in a crossflow rectangular plate-and-frame membrane cell, in which the strains were cultivated on a thin-film composite, polyamide, flat RO membrane coupon (LFC-1) under laminar flow conditions. In the RSPF system, the observed deposition rate of the mucoid strain was between 5- and 10-fold lower than of the wild type using either synthetic wastewater medium (with ionic strength of 14.7 mM and pH 7.4) or 15 mM KCl solution (pH of 6.2). The slower deposition rate of the mucoid strain is explained by 5- to 25-fold increased hydrophilicity of the mucoid strain as compared to the isogenic wild type, PAO1. Corroborating with these results, a significant delay in the onset of biofouling of the RO membrane was observed when the mucoid strain was used as the membrane colonizer, in which the observed time for the induced permeate flux decline was delayed (ca. 2-fold). In conclusion, the lower initial cell attachment of the mucoid strain decelerated biofouling of the RO membrane. Bacterial deposition and attachment is a critical step in biofilm formation and governed by intimate interactions between outer membrane proteins of the bacteria and the surface. Shielding these interactions by a hydrated and hydrophilic alginate capsule is shown to dramatically lessen the biofouling potential of the membrane colonizers.
Communications in Soil Science and Plant Analysis, 2014
Agricultural practices influence the community structure and functional diversity of soil microor... more Agricultural practices influence the community structure and functional diversity of soil microorganisms. In the present study, the impact of nutrient-management systems on the changes in the biological properties of Indian semi-arid Alfisol was assessed. The long-term organically managed (OGF) and inorganically fertilized (IGF) soils from century-old experimental plots were compared for eubacterial diversity using amplicon length heterogeneity PCR (LH-PCR) targeting three hypervariable domains (V1, V1_V2, and V3) of 16S rRNA gene. Of these domains, V1_V2 could discriminate the bacterial communities between the soil types. The relative ratios of amplicons differed between OGF and ICF soils, and eubacterial diversity was decreased substantially because of the inorganic chemical fertilizers, as compared to organic amendments. The Bray–Curtis similarity index and diversity indices of amplicons were greater in OGF soil than in ICF soil. This polyphasic approach revealed that the diversity and functionality of the soil eubacterial community were encouraged by long-term organic manures more than inorganic chemical fertilizers.
A unique nanoelectronic platform, based on single-walled carbon nanotubes (SWNTs), has been fabri... more A unique nanoelectronic platform, based on single-walled carbon nanotubes (SWNTs), has been fabricated for measuring electrical transport in single-molecule DNA. We have tested 80 base pairs of single- and double-stranded DNA (ssDNA and dsDNA, respectively) of complex base sequences. About a 25-40 pA current (at 1 V) was measured for the dsDNA molecule covalently attached to the SWNT electrode at its termini. In the absence of base pair stacking, a ssDNA carries a feeble current of approximately 1 pA or less. Gate-voltage-dependent I-V characteristics revealed that the bridging dsDNA molecule acts as a p-type channel between SWNT source and drain electrodes.
In this paper, we present a new approach that will facilitate the process of drawing meaningful c... more In this paper, we present a new approach that will facilitate the process of drawing meaningful conclusions that are likely to be useful to a biologist who may be interested in only a specific functional aspect of the organism (rather than the entire genome). This is achieved by constructing a comprehensive relational database and an intelligent, userfriendly query system. With the help of simple examples, we show how a biologist with no prior knowledge of databases can use this system. Our database can be queried from the URL: http://biorg.cs.fiu.edu/TFBM/
Pathogenicity of Pseudomonas aeruginosa, a major cause of many acute and chronic human infections... more Pathogenicity of Pseudomonas aeruginosa, a major cause of many acute and chronic human infections, is determined by tightly regulated expression of multiple virulence factors. Quorum sensing (QS) controls expression of many of these pathogenic determinants. Previous microarray studies have shown that the AmpC β-lactamase regulator AmpR, a member of the LysR family of transcription factors, also controls non-β-lactam resistance and multiple virulence mechanisms. Using RNA-Seq and complementary assays, this study further expands the AmpR regulon to include diverse processes such as oxidative stress, heat shock and iron uptake. Importantly, AmpR affects many of these phenotypes, in part, by regulating expression of non-coding RNAs such as rgP32, asRgsA, asPrrF1 and rgRsmZ. AmpR positively regulates expression of the major QS regulators LasR, RhlR and MvfR, and genes of the Pseudomonas quinolone system. Chromatin immunoprecipitation (ChIP)-Seq and ChIP–quantitative real-time polymerase ...
Causal inference in biomedical research allows us to shift the paradigm from investigating associ... more Causal inference in biomedical research allows us to shift the paradigm from investigating associational relationships to causal ones. Inferring causal relationships can help in understanding the inner workings of biological processes. Association patterns can be coincidental and may lead to wrong conclusions about causality in complex systems. Microbiomes are highly complex, diverse, and dynamic environments. Microbes are key players in human health and disease. Hence knowledge of critical causal relationships among the entities in a microbiome, and the impact of internal and external factors on microbial abundance and their interactions are essential for understanding disease mechanisms and making appropriate treatment recommendations. In this paper, we employ causal inference techniques to understand causal relationships between various entities in a microbiome, and to use the resulting causal network to make useful computations. We introduce a novel pipeline for microbiome analy...
Background Bacterial vaginosis (BV) increases the risk of many sexually transmitted infections. T... more Background Bacterial vaginosis (BV) increases the risk of many sexually transmitted infections. The co-occurrence of persistent BV and high-risk HPV (HrHPV) increases the risk of developing cervical cancer. This study aims to investigate the co-occurrence of HrHPV and BV among young women in the US. Methods Stored vaginal swabs were acquired from a previously completed clinical trial. The kinds of bacteria present in the samples were identified by classifying 16S rRNA gene sequences in each sample using high-throughput pyrosequencing. HPV genotyping was performed using quantitative polymerase chain reaction using TaqMan probes in a customized plate (ThermoFisher Scientific; Waltham, Massachusetts). BV was classified using Nugent Scores of Gram Stain. Results Eighty reproductive age African American (AA) women were included in the analysis. The point prevalence of HrHPV was 48.1% (95%CI: 37–59%). The mean age of the participants was 21.4 years (SD: 2.11), 81.2% graduated high school....
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