Natural Sources of Antibacterial Compounds
Antimicrobial resistance (AMR) is one of the most prevalent worldwide public health concerns. The true world burden of AMR is unknown, however, in the United States AMR proves to be fatal in approximately 35,000 people annually and impacts the treatment regime of 2.8 million people.1 In the United States, this results in a higher number of serious infections, increased costs in second-line drugs, and extended hospital admissions.2 With the current trajectory it is estimated that by 2050 AMR will cost upward of 100 trillion USD and claim 10 million lives a year.3
While AMR happens naturally as bacteria adapt to challenging environments, medical misuse, agriculture dependence, and increases in travel, all contribute.2 Of note, six opportunistic pathogens have been recognized as a significant health risk by the Infectious Disease Society of America.4 These multidrug-resistant Gram-positive and Gram-negative bacteria are known as the ESKAPE pathogens, an acronym for Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species.
Although many new antimicrobials have been discovered since the introduction of penicillin in the 1940s, the cost of investment (approximately 1.5 billion USD) and return on that investment (46 million USD per year) has meant many pharmaceutical companies no longer perceive a cost-benefit ratio in research and development. Currently, only four major pharmaceutical companies maintain an active antibiotic research program.5 Furthermore, as the COVID-19 pandemic has shown, the world is not prepared for the threat of infectious diseases, so the development of new antimicrobials is critical. Many antimicrobials are based upon novel compounds derived from nature. Therefore, the focus of my research is on assessing the effectiveness of chemicals isolated from terrestrial plants and soil microorganisms.
Plants as sources of antibacterial compounds
Historically, over 5000 Northern American flora were used for medicinal purposes by its Indigenous peoples.6–8 Many continue to be used today by these same communities. In the laboratory, antimicrobial properties have been demonstrated in some of these species. For example, extracts of Umbellularia californica (California Bay Laurel) inhibits the growth of some Gram-positive bacterial species, including antibiotic-resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA).9 While Salvia apiana (White Sage) is effective against various Gram-positive and Gram-negative bacteria, including Klebsiella and Staphylococcus.10
Despite the wide use by Indigenous communities, the clinical properties of other species remain poorly elucidated. These include Salvia spathacea and Baccharis pilularis. The leaves of S. spathacea, also known as Hummingbird Sage or Pitcher Sage, have historically been used as a decongestant and treatment by the Chumash people.11,12 Baccharis species have been used medicinally by many Indigenous peoples. Historical documentation shows the Indigenous peoples of the Greater San Francisco Bay area used B. douglasii as a disinfectant and B. pilularis as a panacea.13,14 Although Bocek13 states this use was by the Costanoan/Ohlone people, we now know there are many local Indigenous people including the Me-Wuk, Ramaytush and Chochenyo people which may have used these same medicinal herbs.
Soil microbes as sources of antibacterial compounds
Soil is a rich ecosystem with diverse microbial life, and resident microorganisms must adapt to changes in both biotic and abiotic conditions, often by producing a wealth of molecules that inhibit competing microbes. Antimicrobials, therefore, provide an advantage in competing for food and other limited resources. Historically, the soil has provided a wealth of antimicrobial compounds. Almost two decades after penicillin’s discovery, streptomycin was isolated from Streptomyces griseus,15 a soil-dwelling organism. This was quickly followed by chloramphenicol (1947), tetracycline (1948), neomycin (1949), and vancomycin (1950). However, the soil is a heterogeneous environment, where multiple species co-exist. For example, Waksman processed 10,000 samples before identifying streptomycin.16 Thus, isolating new antibiotics from soil microbes is a significant challenge.
The Small World Initiative (SWI)17 is a non-profit organization that uses crowdsourcing to identify new antibiotics in the diverse soil population. My research group is collaborating with SWI on this project.
First-year and second-year students in my laboratory can follow a Course-Based Undergraduate Research Experience (CURE). CUREs support the retention of students and offer early opportunities to engage in research. Those with microbiology experience can omit the CURE experience, and often become mentors in their senior year. Currently, my laboratory has six undergraduate students.
Persistence in Science, Technology, Engineering, and Math
Nationally, the number of women in science and engineering has risen.18 However, women who are Black, Latinx, American Indian or Alaskan Natives remain underrepresented in Science, Technology, Engineering, and Math (STEM).19 Those of Asian descent are also challenged: they remain underrepresented in STEM leadership and are often burdened with stereotypes.20 In 2015, the diversity in STEM at our institution was much lower (8%) compared with the college average (54%). However, this number has improved significantly (63%) and is now comparable to the college-wide average of 65%.
In 2016, I was awarded a National Science Foundation Scholarships in STEM (S-STEM)* grant to design modalities that increased student retention and persistence to degree completion for underrepresented students. This program expanded the work of the Hellman Summer Science and Math program (HSSM), as well as other existing structures, and deployed new support systems.
HSSM is a summer bridge residential initiative that has varied from two to four weeks since its inception in 2007. It provides students with a rigorous academic transition to college in which they prepare for lectures and laboratories while they also learn how to manage their study time. The goal is to engage students in the excitement of learning about STEM, while simultaneously providing tools for success. HSSM students participate in approximately 15 hours of class time across three-course modules (math, chemistry, and biology) and 12 hours of laboratory work per week. This is complemented by 10 hours per week of structured study time, interspersed with leadership development and team-building activities, introductions to key resources on campus, and weekly educational and social outings. During the fall semester, students also engage in a community engagement project. Throughout, cohort connection is emphasized and maintained through one-on-one advising and group meetings.
One of the new modalities of the NSF S-STEM grant was to integrate workshops into the student experience as they have a positive influence on the academic and social engagement of underrepresented students.21 The planned NSF workshops followed a sequence from college skills to career exploration. They included workshops on imposter syndrome, stereotype threat, as well as on resumes, and cover letters. In addition, within underrepresented communities, there is a long history of celebrating role models, where they offer inspiration.22–24Additional role models, to those of our diverse faculty, were therefore provided by the Women in STEM lecture series, which introduced our scholars to individuals working in industry or academia.
Each student received a scholarship to offset their financial need with the hope it would reduce the number of hours spent generating income through additional sources. However, it should be noted many of these students, even with this scholarship, still work, impacting the time spent on academics.
Student-focused strategies for STEM retention
Understanding how students learn and why they persist, particularly in STEM fields, is of critical importance to changing the landscape of our disciplines. Unfortunately, many institutions attempt to shift from ingrained programs by adding one or two new strategies and neglect the comprehensive experience the student faces. My research focuses on considering programming, strategies for retention, and inclusion as integrated pieces of student support. Ultimately, programs must be more dynamic to reflect best practices for the current population of STEM students.
This summer bridge program, HSSM, has contributed significantly to our retention of students. Together, through cohort building, workshops, extracurricular experiences, thoughtful mentoring, and advice, I have increased the 4-year graduation rate of the college (57%) to 81%. Our STEM students therefore enter graduate school or employment much faster and incur less debt. Furthermore, by constantly revising the program, I support the current needs of our students, especially those from underrepresented groups. Of my graduating students, 77% are people of color and 30% are first-generation. A manuscript describing this work is currently being developed for publication. In addition, we enrolled two NSF S-STEM cohorts, one in 2016 and one in 2017. While the outcomes are being analyzed both quantitatively and qualitatively, and statistical analysis is limited due to the size of the cohort, we graduated 100% of cohort 1, all with STEM degrees, in May 2020. Cohort 2 is also on the way to graduate with STEM degrees.
* This work is supported by the National Science Foundation under Grant No. 1565160. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation.
- Centers for Disease Control and Prevention (U.S.). Antibiotic resistance threats in the United States, 2019. (2019).
- Dadgostar, P. Antimicrobial Resistance: Implications and Costs. Infect. Drug Resist. 12, 3903–3910 (2019).
- O’Neill, J. Tackling drug-resistant infections globally. (2016).
- Boucher, H.W. et al. Bad Bugs, No Drugs: No ESKAPE! An Update from the Infectious Diseases Society of America. Clin. Infect. Dis. 48, 1–12 (2009).
- Plackett, B. Why big pharma has abandoned antibiotics. Nature 586, S50–S52 (2020).
- Stockwell, C. Natureʾs pharmacy: a history of plants and healing. (Century, 1988).
- Borchers, A.T. et al. Inflammation and Native American medicine: the role of botanicals. Am. J. Clin. Nutr. 72, 339–347 (2000).
- Moerman, D.E. An analysis of the food plants and drug plants of native North America. J. Ethnopharmacol. 52, 1–22 (1996).
- Carranza, M.G. et al. Antibacterial activity of native California medicinal plant extracts isolated from Rhamnus californica and Umbellularia californica. Ann. Clin. Microbiol. Antimicrob. 14, 29 (2015).
- Afonso, A.F. et al. The Health-Benefits and Phytochemical Profile of Salvia apiana and Salvia farinacea var. Victoria Blue Decoctions. Antioxidants 8, 241 (2019).
- Timbrook, J. Chumash ethnobotany: plant knowledge among the Chumash people of southern California. (Santa Barbara Museum of Natural History; Heyday Books, 2007).
- Dye, C. & Crane, A. California Native Medicinal Plants. (2017).
- Bocek, B.R. Ethnobotany of Costanoan Indians, California, based on collections by John P. Harrington. Econ. Bot. 38, 240–255 (1984).
- BRIT – Native American Ethnobotany Database. http://naeb.brit.org/.
- Schatz, A. et al. Streptomycin, a Substance Exhibiting Antibiotic Activity Against Gram-Positive and Gram-Negative Bacteria. Proc. Soc. Exp. Biol. Med. 55, 66–69 (1944).
- McKenna, M. Hunting for Antibiotics in the World’s Dirtiest Places. The Atlantic.
- Hernandez, S. et al. J. Small world initiative. (2016).
- The United States Census Bureau. Disparities in STEM Employment by Sex, Race, and Hispanic Origin.
- National Science Foundation. Women, Minorities, and Persons with Disabilities in Science and Engineering.
- McGee, E. “Black Genius, Asian Fail”: The Detriment of Stereotype Lift and Stereotype Threat in High-Achieving Asian and Black STEM Students. AERA Open 4 (2018).
- Dumas-Hines, F.A. et al. Promoting diversity: recommendations for recruitment and retention of minorities in higher education. Coll. Stud. J. 35, 433–442 (2001).
- Aronson, J. et al. Reducing the Effects of Stereotype Threat on African American College Students by Shaping Theories of Intelligence. J. Exp. Soc. Psychol. 38, 113–125 (2002).
- Lockwood, P. “Someone Like Me can be Successful”: Do College Students Need Same-Gender Role Models? Psychol. Women Q. 30, 36–46 (2006).
- Young, D.M. et al. The Influence of Female Role Models on Women’s Implicit Science Cognitions. Psychol. Women Q. 37, 283–292 (2013).