Search or add a thesis

Advanced Search (Beta)
Home > Characterization of Drug Resistance-Associated Mutations and Genetic Diversity in Mycobacterium Tuberculosis Isolates from Khyber Pakhtunkhwa, Pakistan

Characterization of Drug Resistance-Associated Mutations and Genetic Diversity in Mycobacterium Tuberculosis Isolates from Khyber Pakhtunkhwa, Pakistan

Thesis Info

Access Option

External Link

Author

Idrees, Muhammad

Program

PhD

Institute

University of Peshawar

City

Peshawar

Province

KPK

Country

Pakistan

Thesis Completing Year

2018

Thesis Completion Status

Completed

Subject

Biotechnology

Language

English

Link

http://prr.hec.gov.pk/jspui/bitstream/123456789/11143/1/Muhammad%20Idrees_Biotech_2018_UoPsw_PRR.pdf

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676725684451

Asian Research Index Whatsapp Chanel
Asian Research Index Whatsapp Chanel

Join our Whatsapp Channel to get regular updates.

Similar


The Khyber Pakhtunkhwa region of Pakistan has been known for a high burden of tuberculosis (TB). However, there is little information about the molecular characteristics of Mycobacterium tuberculosis (M. tuberculosis) strains predominant in the province. Therefore, this study was planned to study the genetic diversity and molecular patterns responsible for the extensive drug resistance in the M. tuberculosis isolates isolated from clinical samples. In the current study total 794 patients were tested for suspected tuberculosis by fluorescence microscopy and GeneXpert system at the Provincial TB Reference Laboratory, Khyber Pakhtunkhwa, Pakistan. Among the 794 patients studied, 170 samples gave positive results and were further tested for drug susceptibility, out of which 163 samples gave results of drug susceptibility test. Among these 163 isolates, 79 (48.46%) were resistant to isoniazid, 47 (28.83%) were resistant to streptomycin, 56 (34.35%) were resistant to rifampicin, 31 (19.01%) were resistant to ethambutol, 16 (9.81%) were resistant to pyrazinamide, 59 (36.1%) were resistant to ofloxacin, 12 (7.36%) were resistant to capreomycin and 11 (6.74%) were resistant to amikacin. Further, these resistant isolates were selected for mutation analysis in the ‘hot spot regions’ of katG, rpoB, inhA, rpsL, embB, pncA, gyrA and gyrB genes. For the mutation analysis of the hotspot regions of katG and inhA genes, 30 resistant isolates were selected randomly. Among these 30 isolates, 21 (70%) had a mutation in katG gene and two (6.6%) had the most common C15T mutation in inhA promoter region. In 21 katG mutant isolates, 15 showed Ser315Thr, three showed Gly316Ser, two showed Ser315Arg mutations while one isolate was positive for a double mutation of Ser303Trp and Lys274Arg. Fourteen isolates were analyzed for the rpoB gene mutation. The mutations detected in rpoB gene in the selected isolates were Ser450Leu, Asp435Gly, Ser450Gln, Gly455Asp and Pro454His. Sixteen isolates were analyzed for streptomycin resistant-mutation in the rpsL gene. The rpsL gene mutations detected in six isolates were Lys43Arg, Lys88Arg, and Lys111Ile. Sixteen isolates were analyzed for ethambutol resistant-mutations of the embB gene. Out of these, 10 isolates were positive for Ala281val, Met306Leu, and Met306Val mutations. Eight isolates were analyzed for pyrazinamide resistant mutations of the pncA gene. Among them, 5 isolates showed a mutation in pncA gene, which included Gln141Pro, Ser65Ser*, Gly132Ser and Cys138stop mutations. The insertion of G at position 392 was also detected in pncA gene. Twenty isolates were analyzed for ofloxacin resistant mutations in gyrA and gyrB genes. Asp94Gly mutation in gyrA gene was detected in nine isolates while no mutation for the gyrB gene was detected in the selected isolates. These findings provide insights into the genetic variability existing against various drugs in M. tuberculosis circulating in Khyber Pakhtunkhwa, Pakistan. The results showed some novel mutations in the genes, katG, rpoB, rpsL and pncA. Small molecule inhibitors of the proteins encoded by the drug resistant genes, i.e., KatG, gyrA, pncA and rpoB of M. tuberculosis, were identified using computational methods. On the basis of the docking score and binding interactions, ten small molecule compounds were identified as novel inhibitors of each protein. These compounds showed significant interaction with the active site of the protein. The genetic diversity of M. tuberculosis isolates was estimated using RAPD and PCR restriction enzyme analysis.Fifty-two MTBC isolates were randomly selected for RAPD-PCR and PCR-restriction enzyme analysis. M. Bovis and M. tuberculosis H37Rv were used as reference strains. RAPD-PCR differentiated the strains and authenticated the high molecular diversity.PCR restriction enzyme analysis (PRA) profiles of all isolates and reference strains were found to be the same. High diversity values were found in the studied area implying high population diversity of M. tuberculosis that’s being prevalent in Khyber Pakhtunkhwa, Pakistan. The development of M. tuberculosis resistant strains is a major challenge severely affecting public health worldwide. New drugs obtained from natural resources could be a viable option to avoid serious drug resistance issues. On this quest, Aspergillus and Penicillium spp. were isolated from the surface soil. The secondary metabolites of Aspergillus and Penicillium were screened for anti-tuberculosis activity. The secondary metabolites of Aspergillus were active against M. tuberculosis whereas those of Penicillium showed no significant inhibitory activity. The results provide an overview of the existing nature of Multi drug resistance in M. tuberculosis circulating in Khyber Pakhtunkhwa province of Pakistan.
Loading...
Loading...

Similar Books

Loading...

Similar Chapters

Loading...

Similar News

Loading...

Similar Articles

Loading...

Similar Article Headings

Loading...

پنڈت کشن پرشاد کول

پنڈت کشن پرشاد کول
پنڈت کشن پرشادکول لکھنؤ کے رہنے والے اور لکھنؤ کی پُرانی تہذیب اور روایات کی بڑی حسین یادگار تھے، اُردو زبان کے نکتہ سنج ونکتہ شناس، بلند پایہ ادیب اور بڑے صحیح الخیال اورنیک دل بزرگ تھے۔اُردو زبان اوراس کے ساتھ وابستہ کلچر اورتہذیب کے ساتھ اُن کوعشق تھا۔ یوپی میں اُردو کو علاقائی زبان بنانے کے لیے دستخطی مہم کی کامیابی زیادہ ترانھیں کی کوششوں کانتیجہ تھی۔اُردو سے متعلق ہرتحریک میں وہ سرگرمی سے حصّہ لیتے تھے۔ چنانچہ وفات سے کچھ دن پہلے ہی انھوں نے بہار میں اردو کانفرنس کی صدارت کی تھی اوراس میں بڑا اچھا خطبہ پڑھا تھا۔ اگرچہ وہ اب خود دنیا میں نہیں ہیں لیکن اپنے کردار وعمل اوراپنے اخلاق کاایک ایسا نقش چھوڑگئے ہیں کہ نئی نسلیں اُن سے بہت کچھ سبق حاصل کرسکتی ہیں۔ [ فروری ۱۹۵۵ء]

 

السلم و السلام و تطبيقا تھا في ضوء السيرة النبوية

There is no doubt that Islam is a religion of peace which ensures peace regionally and globally in the light of its teachings. It is not only a religion of worship, but it is a religion includes ethics and caring for others and takes care of the rights of individuals as well as society. The life of Prophet Muhammad, r is the best role model in creating world peace atmosphere as He had ordered his followers and believers to realize peace in their societies. Islam guarantees peace even in war situation as it provides full protection and refuge to all those innocents who do not participate in the war. It is not unknown now that the contemporary world is witnessing events that souls hate and hearts alienate which caused racisms and populism and that their effects threatened communities and destroy firm foundations of peace. So in this contemporary perspective, the importance of research and writing about world peace increases subject to all of the studies levels, whether in universities or conferences especially in light of the biography of Holy Prophet Muhammad r. In this research, I will focus on the following points: Peace and its practical examples in of Holy Prophet Muhammad r. Explanation about the concept of peace and its practice in life of Holy Prophet Muhammad r. Clarifying the most prominent contemporary security challenges in the light of the Prophet's biography. Discussion on common misconceptions about Global peace matter and their correction in the sacred Biography of the Prophet Muhammad r

Implication of Cultural Psychology on Individual Behavioral Patterns: Khaled Hosseinis's Art of Characterization

Implication of Cultural Psychology on Individual Behavioral Patterns: Khaled Hosseinis's Art of Characterization This thesis offers its readers a detailed analysis of Khaled Hosseini’s later work from the perspective of Cultural Psychology. Its underline purpose is to explore the psychological and behavioral mechanisms of the characters in the fictional world of Hosseini keeping in mind the socio-cultural strands of their indigenous environment. This research also strongly challenges the post-modern notion of a single “universal culture” and negates the attempts of the developed countries to suppress the individuality of the weaker nations in the name of cultural uniformity. In this way this is a step forward to voice cultural identity of the much suppressed and devastated Afghan nation. Being an honest voice of his native land and a faithful representative of the emotionally and physically shattered people of Afghanistan Hosseini’s later writings including A Thousand Splendid Suns (2007) and And the Mountains Echoed (2013) depict both the rich customs and traditions of his mother-land as well as the atrocities and injustice committed by the narrow- minded male part of the society in the name of religion and family honor. Hence the work chosen for this particular research are a perfect blend of endurance and sufferings of the local Afghan population. A Qualitative research procedure has been opted to examine Hosseini’s art of characterization through the actions and dialogues of his characters. This can also be taken as a Case Study of Hosseini’s work focusing upon the symbolism, imagery and the language used in the selected novels. It explores the depiction of Afghan society and the supremacy of the native socio-cultural standards as the controlling factor in the lives of their practitioners. Hence it asserts that the psychological and behavioral patterns of an individual are not related to one’s genetic make-up or biological inheritance rather it is an immediate native culture that shapes one’s acting and thinking patterns. Therefore for the cultural evolution or the social development of the masses the psychological and behavioral mechanisms of the individuals as well as the norms and traditions of a particular culture have to work in collaboration and only then any nation can fulfill her dream of rapid growth and expansion.