Challenges in Drug Discovery for Intracellular Bacteria
Novel drugs are needed to treat a variety of persistent diseases caused by intracellular bacterial pathogens. Virulence pathways enable many functions required for the survival of these pathogens, including invasion, nutrient acquisition, and immune evasion. Inhibition of virulence pathways is an es...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-09-01
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| Series: | Pathogens |
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| Online Access: | https://www.mdpi.com/2076-0817/10/9/1172 |
| _version_ | 1797517633763934208 |
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| author | Allison N. Tucker Travis J. Carlson Aurijit Sarkar |
| author_facet | Allison N. Tucker Travis J. Carlson Aurijit Sarkar |
| author_sort | Allison N. Tucker |
| collection | DOAJ |
| description | Novel drugs are needed to treat a variety of persistent diseases caused by intracellular bacterial pathogens. Virulence pathways enable many functions required for the survival of these pathogens, including invasion, nutrient acquisition, and immune evasion. Inhibition of virulence pathways is an established route for drug discovery; however, many challenges remain. Here, we propose the biggest problems that must be solved to advance the field meaningfully. While it is established that we do not yet understand the nature of chemicals capable of permeating into the bacterial cell, this problem is compounded when targeting intracellular bacteria because we are limited to only those chemicals that can permeate through both human and bacterial outer envelopes. Unfortunately, many chemicals that permeate through the outer layers of mammalian cells fail to penetrate the bacterial cytoplasm. Another challenge is the lack of publicly available information on virulence factors. It is virtually impossible to know which virulence factors are clinically relevant and have broad cross-species and cross-strain distribution. In other words, we have yet to identify the best drug targets. Yes, standard genomics databases have much of the information necessary for short-term studies, but the connections with patient outcomes are yet to be established. Without comprehensive data on matters such as these, it is difficult to devise broad-spectrum, effective anti-virulence agents. Furthermore, anti-virulence drug discovery is hindered by the current state of technologies available for experimental investigation. Antimicrobial drug discovery was greatly advanced by the establishment and standardization of broth microdilution assays to measure the effectiveness of antimicrobials. However, the currently available models used for anti-virulence drug discovery are too broad, as they must address varied phenotypes, and too expensive to be generally adopted by many research groups. Therefore, we believe drug discovery against intracellular bacterial pathogens can be advanced significantly by overcoming the above hurdles. |
| first_indexed | 2024-03-10T07:19:15Z |
| format | Article |
| id | doaj.art-5f5e27c0281a40c6b67a833aec6b54cc |
| institution | Directory Open Access Journal |
| issn | 2076-0817 |
| language | English |
| last_indexed | 2024-03-10T07:19:15Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pathogens |
| spelling | doaj.art-5f5e27c0281a40c6b67a833aec6b54cc2023-11-22T14:42:50ZengMDPI AGPathogens2076-08172021-09-01109117210.3390/pathogens10091172Challenges in Drug Discovery for Intracellular BacteriaAllison N. Tucker0Travis J. Carlson1Aurijit Sarkar2Fred Wilson School of Pharmacy, High Point University, One University Parkway, High Point, NC 27268, USAFred Wilson School of Pharmacy, High Point University, One University Parkway, High Point, NC 27268, USAFred Wilson School of Pharmacy, High Point University, One University Parkway, High Point, NC 27268, USANovel drugs are needed to treat a variety of persistent diseases caused by intracellular bacterial pathogens. Virulence pathways enable many functions required for the survival of these pathogens, including invasion, nutrient acquisition, and immune evasion. Inhibition of virulence pathways is an established route for drug discovery; however, many challenges remain. Here, we propose the biggest problems that must be solved to advance the field meaningfully. While it is established that we do not yet understand the nature of chemicals capable of permeating into the bacterial cell, this problem is compounded when targeting intracellular bacteria because we are limited to only those chemicals that can permeate through both human and bacterial outer envelopes. Unfortunately, many chemicals that permeate through the outer layers of mammalian cells fail to penetrate the bacterial cytoplasm. Another challenge is the lack of publicly available information on virulence factors. It is virtually impossible to know which virulence factors are clinically relevant and have broad cross-species and cross-strain distribution. In other words, we have yet to identify the best drug targets. Yes, standard genomics databases have much of the information necessary for short-term studies, but the connections with patient outcomes are yet to be established. Without comprehensive data on matters such as these, it is difficult to devise broad-spectrum, effective anti-virulence agents. Furthermore, anti-virulence drug discovery is hindered by the current state of technologies available for experimental investigation. Antimicrobial drug discovery was greatly advanced by the establishment and standardization of broth microdilution assays to measure the effectiveness of antimicrobials. However, the currently available models used for anti-virulence drug discovery are too broad, as they must address varied phenotypes, and too expensive to be generally adopted by many research groups. Therefore, we believe drug discovery against intracellular bacterial pathogens can be advanced significantly by overcoming the above hurdles.https://www.mdpi.com/2076-0817/10/9/1172intracellular bacteriavirulencepersistencedrug discoveryinfection |
| spellingShingle | Allison N. Tucker Travis J. Carlson Aurijit Sarkar Challenges in Drug Discovery for Intracellular Bacteria Pathogens intracellular bacteria virulence persistence drug discovery infection |
| title | Challenges in Drug Discovery for Intracellular Bacteria |
| title_full | Challenges in Drug Discovery for Intracellular Bacteria |
| title_fullStr | Challenges in Drug Discovery for Intracellular Bacteria |
| title_full_unstemmed | Challenges in Drug Discovery for Intracellular Bacteria |
| title_short | Challenges in Drug Discovery for Intracellular Bacteria |
| title_sort | challenges in drug discovery for intracellular bacteria |
| topic | intracellular bacteria virulence persistence drug discovery infection |
| url | https://www.mdpi.com/2076-0817/10/9/1172 |
| work_keys_str_mv | AT allisonntucker challengesindrugdiscoveryforintracellularbacteria AT travisjcarlson challengesindrugdiscoveryforintracellularbacteria AT aurijitsarkar challengesindrugdiscoveryforintracellularbacteria |