Genomics of Infectious Disease: University Research Report

This report provides a comprehensive overview of the genomics of infectious diseases. It begins by explaining how genomic sequence data is used to track infectious diseases, highlighting the role of next-generation sequencing (NGS) in understanding pathogen virulence, cross-infections, and mutation analysis. The report then examines the action of drugs in controlling infections, specifically focusing on HIV and tuberculosis, and discusses the molecular basis of organism drug resistance in various diseases. Furthermore, it explores the application of genome sequencing in infectious disease diagnostics, treatment, and the development of vaccines, emphasizing the identification of genetic changes and the importance of whole-genome sequencing (WGS) in understanding drug resistance mechanisms. The report also references several studies and research papers, including those focusing on bacterial genome sequencing and the impact of WGS on disease management and drug development.

Running head: GENOMICS OF INFECTIOUS DISEASE
Genomics of Infectious Disease
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Table of Contents
Tracking of infectious disease by Genomic Sequence data..........................................................2
Action of drugs in controlling infections of H.I.V, T.B.....................................................................2
Molecular basis of organism drug resistance in some diseases...................................................3
Application of genome sequence in infectious disease.................................................................4
References....................................................................................................................................6

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Tracking of infectious disease by Genomic Sequence data
With the advent of the revolution of the next generation whole genome sequencing of wide
varieties of a pathogen, the molecular diagnostics of infections has made an outbreak. The next
generation sequencing uses the DNA sequence and determines the data of information in a
complete run. These data can be used to understand the virulence, cross-infections and the
mode of infections in the pathogens. The next generation sequencing platforms like the
Miseq( Illumina) and Ion PGM are mainly used to generate the sequences of the required
pathogens. The sequencing data would then be analyzed by the software tools for the
optimization. The sequence analysis will help to find out the genetic conditions of the pathogens
during infections. The epidemiological monitoring of the cross infection in the pathogens can be
studied by studying genome sequence data (1). The genome sequence data will also give the
phylogenetic relationship among the similar group of pathogens and find the mutation in the
genes that have lead to the cross infection or the infection in the host. The metabolic changes
and the housekeeping functions can be traced with the use of the data. Thus NGS or the next
generation sequence that will involve the comparison of huge data of micro organisms may
shed some light n the evolution and the population genetics of the disease. By comparing
several samples from the population one can easily identify the root change that causes to
cross infection in a population. The real reason behind the infections and the transmission of the
disease can be understood through the genome data of the pathogens. Genome sequences will
identify the phenotypic and the genotypic changes of the pathogens that confirm with the
dynamics of infection. Thus this will help to develop a more strategic plan for the prevention,
treatment, and designing of vaccines. Haemophilus is the first pathogen whose genome was
sequenced. This has identified that in human disease A and B subtypes are defined by the
hemagglutanin and neuraminidase which has significant roles in the novel therapeutics and
diagnosis. Limitation in Whole genome sequencing is that it can give information of the
sequence of one pathogen at one time (2).
Action of drugs in controlling infections of H.I.V, T.B
The virus of Human immunodeficiency spreads in an alarming manner. Despite such a
spread of the disease, the countries have now adapted the drugs that have hugely controlled
the transmission. The virus in H.I.V attacks the CD4 cells, T cells. Thus the number of T cells
get lowered and the make the immune system harder to guard against the diseases. The main

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drugs that can be useful in the action against the Aids actions are the Abacavir, Didanosine
which has the action against the reverse transcriptase the enzyme that retrovirus of the H.I.V
virus use for its genome multiplication (3). The action of drugs will include the control of growth
of the virus and improves the work of the immune system. These drugs are proven to have
fewer side effects than others. These drugs are also called the ‘non-jukes” that binds to the
specific proteins of the virus and prevents their replication. The protease inhibitors drugs could
be used like the Atazanavir that blocks the proteins that the infected cells require to put
together(4).
Isoniazid is the approved drug used in the treatment of the patients with Tuberculosis. The
other drugs are the rifampicin, ethambutol. The exact mechanism of the action of drugs like
isoniazid is unknown. However, it is known that the antibiotic prevents Mycobacterium from
making substances like mycolic acids, which are necessary for the formation of the cell wall in
bacteria. It binds with the enzymes that interfere with the cell metabolism of the bacteria. Thus
the disruption of the cellular metabolism and the cell wall will kill the bacteria (5). However,
pharmacologically the action of Isoniazid varies among different people with different genomic
variants. Isoniazid may have side effects like fatal liver diseases, hepatitis. Recently multiple
drug therapies are used to treat T.B (6).
Molecular basis of organism drug resistance in some diseases
Bacterial species are tremendously being resistant to huge spectrum of antibiotics. Some of
the bacterial strains like the Streptococcus pneumonia are resistant to benzylpenicillin. Antibiotic
drug resistance is the main cause of the clinical resistance in the hospitals. The antibiotic
resistance occurs due to the action of the prevention of the antibiotics to enter the cells or
pumping it out faster through the hollow tube or porin. Increased efflux of the drugs occurs by
the energy-requiring transport pump which is recognized mechanism of tetracyclines. The
molecular epidemiology of resistance genes shows that the development of the resistance
occurs by the mutation or acquisition of new genes. The mutation is spontaneous that has lead
to increased efflux or the prevention of entry of the drugs (7). The favorable mutations that have
occurred are due to transposons and the insertion sequences are the molecular basis of the
drug resistance. DNA sequencing has shown that the Beta- lactamases and aminoglycoside
gene mutations have mainly contributed to the resistance. There might have been gene
exchange occurred that must have changed the genome structure of the pathogens making
them unaffected with the drugs (8).

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This will be a direction of a new field of research in a drug. Genome sequence data can be
useful to identify the genes that have been acquired or lost due to which they had become
resistant. The evolution of these drug resistant bacteria can be considered as one of the
discoveries that can if reduced can help treat a wide spectrum of infectious disease (9). The
complicated molecular mechanisms of the drug resistance genes and their diverged functions
can only be identified by looking deep within the genome sequence data. The genome
sequences will reveal their complex and surprising nature of the biosynthetic pathways,
evolution and biochemical modes of action. Thus in drug research, it will in future help design
therapeutic drugs that can target several drug resistant diseases.
Application of genome sequence in infectious disease
The genomic is helping in the development of more accurate, effective and personalized way
of accessing the infections by the pathogens. Genetic sequencing technologies helping in
further understanding the mechanism of interaction of the pathogens with the host, contribution
to the pathogenicity in immune responses. Whole genome sequences will prepare the
epidemiological data that will help design the public health interventions by looking into their
mechanism of evolution that has contributed to their pathogenicity. This will be equally useful in
identifying the transmission dynamics of the pathogens(10).
Different people show differences in response to a particular drug. The genome sequences of
the pathogens will help identify the treatment profile that can be suitable for a patient to kill
them. Since the whole genome sequence will identify the phenotype and the genotype change
the drug selection can be made accurate with it. Whole genome sequencing will identify the
molecular basis of the action of particular drugs and identify the changes in the biochemical and
metabolic pathways by giving the genomic sequence data. One can easily identify the enzymes
or the proteins that are being new to the genomic profile. Such virulent proteins if targeted could
be the best approach to treat any pathogens with molecular level drugs. WGS will also be useful
for the surveillance of the pathogenicity and the transmission of the diseases(11).
WGS has also identified the wide range of pathogens is being inactive to the presence of
drugs. One such growing concern is with the antibiotic resistance bacteria. WGs has become a
diagnostic tool that will be useful in the future for new sets of drugs. Genome sequences have
also identified the resistance mechanisms, particularly with tuberculosis. In tuberculosis WGS
sequencing by using pyrosequencing techniques have identified the F0 subunit of the ATP
synthase which has been mutated and has lead to such change in the drug resistance
mechanisms. It has been identified for example that the synonymous mutation in Rv3792 has

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contributed to the drug resistance of Escherichia coli. The genetic basis has been found that the
increase in ethambutol has increased the expression of the embed that has conferred
resistance. Subsequently, similar mechanisms have been identified for the resistance of
isoniazid and ethanamide cross resistance in MTBC. In this case, the synonymous mutations in
the mabA create an alternative promoter for inhA (12).
In addition to that, the WGS can be used in the human management of diseases. This is
because of the reason that it is a tool being used in the clinical trials. It is used extensively to
distinguish reinfection from the exogenous source and to the relapse of the primary infection.
This is very important for understanding the efficiency of the drugs and to find the details of the
regime of any drug under investigation. WGS will give the complete gene repertoires of the
pathogens and identify the single nucleotide polymorphism or the changes due to a mutation
that has to lead to such a change in the drug resistance.

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References
1. Kumar N, Miyajima F, He M, Roberts P, Swale A, Ellison L, Pickard D, Smith G,
Molyneux R, Dougan G, Parkhill J. Genome-based infection tracking reveals dynamics
of Clostridium difficile transmission and disease recurrence. Clinical infectious diseases.
2015 Dec 18;62(6):746-52.
2. Loman NJ, Pallen MJ. Twenty years of bacterial genome sequencing. Nature reviews.
Microbiology. 2015 Dec 1;13(12):787.
3. Stucki D, Ballif M, Bodmer T, Coscolla M, Maurer AM, Droz S, Butz C, Borrell S, Längle
C, Feldmann J, Furrer H. Tracking a tuberculosis outbreak over 21 years: strain-specific
single-nucleotide polymorphism typing combined with targeted whole-genome
sequencing. The Journal of infectious diseases. 2014 Oct 30;211(8):1306-16.
4. Wells WA, Boehme CC, Cobelens FG, Daniels C, Dowdy D, Gardiner E, Gheuens J,
Kim P, Kimerling ME, Kreiswirth B, Lienhardt C. Alignment of new tuberculosis drug
regimens and drug susceptibility testing: a framework for action. The Lancet infectious
diseases. 2013 May 31;13(5):449-58.
5. Lechartier B, Rybniker J, Zumla A, Cole ST. Tuberculosis drug discovery in the post‐
post‐genomic era. EMBO molecular medicine. 2014 Jan 8:e201201772.
6. Menéndez-Arias L. Molecular basis of human immunodeficiency virus type 1 drug
resistance: overview and recent developments. Antiviral research. 2013 Apr 30;98(1):93-
120.
7. Ling LL, Schneider T, Peoples AJ, Spoering AL, Engels I, Conlon BP, Mueller A,
Schäberle TF, Hughes DE, Epstein S, Jones M. A new antibiotic kills pathogens without
detectable resistance. Nature. 2015 Jan 22;517(7535):455-9.
8. Van Acker H, Van Dijck P, Coenye T. Molecular mechanisms of antimicrobial tolerance
and resistance in bacterial and fungal biofilms. Trends in microbiology. 2014 Jun
30;22(6):326-33.
9. Palmer AC, Kishony R. Understanding, predicting and manipulating the genotypic
evolution of antibiotic resistance. Nature reviews. Genetics. 2013 Apr;14(4):243.
10. Holt KE, Wertheim H, Zadoks RN, Baker S, Whitehouse CA, Dance D, Jenney A,
Connor TR, Hsu LY, Severin J, Brisse S. Genomic analysis of diversity, population
structure, virulence, and antimicrobial resistance in Klebsiella pneumoniae, an urgent
threat to public health. Proceedings of the National Academy of Sciences. 2015 Jul
7;112(27):E3574-81.

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11. Roetzer A, Diel R, Kohl TA, Rückert C, Nübel U, Blom J, Wirth T, Jaenicke S, Schuback
S, Rüsch-Gerdes S, Supply P. Whole genome sequencing versus traditional genotyping
for investigation of a Mycobacterium tuberculosis outbreak: a longitudinal molecular
epidemiological study. PLoS medicine. 2013 Feb 12;10(2):e1001387.
12. Farrer RA, Henk DA, Garner TW, Balloux F, Woodhams DC, Fisher MC. Chromosomal
copy number variation, selection and uneven rates of recombination reveal cryptic
genome diversity linked to pathogenicity. PLoS genetics. 2013 Aug 15;9(8):e1003703.