I am a general surgery resident at Stanford Hospital. I am interested in surgical health services research and access to and outcomes of surgical care in underserved populations, both in the US and abroad.
The Affordable Care Act's Insurance Marketplace Subsidies Were Associated With Reduced Financial Burden For US Adults.
Health affairs (Project Hope)
2021; 40 (3): 496–504
Research suggests that the Affordable Care Act (ACA) Medicaid expansions improved financial protection for the poor. However, evidence is limited on whether subsidies offered through the ACA Marketplaces, the law's other major coverage expansion, were associated with reduced financial burden. Using national survey data from the period 2008-17, we examined changes in household health care spending among low-income adults eligible for both Marketplace premium subsidies and cost-sharing reductions (139-250percent of the federal poverty level) and middle-income adults eligible only for premium subsidies (251-400percent of the federal poverty level), using high-income adults ineligible for subsidies (greater than 400percent of the federal poverty level) as controls. Among low-income adults, Marketplace subsidy implementation was associated with 17percent lower out-of-pocket spending and 30percent lower probability of catastrophic health expenditures. In contrast, middle-income adults did not experience reduced financial burden by either measure. These findings highlight the successes and limitations of Marketplace subsidies as debate continues over the ACA's future.
View details for DOI 10.1377/hlthaff.2020.01106
View details for PubMedID 33646874
- Catastrophic Health Expenditures Across Insurance Types and Incomes Before and After the Patient Protection and Affordable Care Act. JAMA network open 2020; 3 (9): e2017696
Catastrophic expenditures in California trauma patients after the Affordable Care Act: reduced financial risk and racial disparities.
American journal of surgery
BACKGROUND: Hospital charges due to major injury can result in high out-of-pocket expenses for patients. We analyzed the effect of the Affordable Care Act (ACA) on catastrophic health expenditures (CHE) among trauma patients.METHODS: We identified trauma patients aged 19-64 admitted to a safety-net Level 1 trauma center in California from 2007 to 2017. Out-of-pocket expenditures and income were calculated using hospital charges, insurance status, and ZIP code. CHE was defined using the World Health Organization definition of out-of-pocket spending exceeding 40% of inflation-adjusted income minus food and housing expenditures. Multivariable logistic regression was performed to assess odds of CHE post-ACA (2014-2017) vs. pre-ACA (2007-2013).RESULTS: Of 7519 trauma patients, 20.6% experienced CHE, including 89.0% of uninsured patients. There was a 74% decrease in odds of CHE post-ACA (aOR: 0.26, 95% CI: 0.22-0.30), with greater decreases among Black (aOR: 0.09, 95% CI: 0.04-0.18) and Hispanic (aOR: 0.23, 95% CI: 0.19-0.29) patients.CONCLUSIONS: ACA implementation was associated with markedly decreased odds of catastrophic expenditures and decreased racial disparities in financial protection among trauma patients in our study.
View details for DOI 10.1016/j.amjsurg.2020.04.012
View details for PubMedID 32354603
Impact of the Affordable Care Act Insurance Marketplaces on Out-of-Pocket Spending Among Surgical Patients.
Annals of surgery
OBJECTIVE: To evaluate the association between the introduction of the Affordable Care Act (ACA) Health Insurance Marketplaces ("Marketplaces") and financial protection for patients undergoing surgery.BACKGROUND: The ACA established Marketplaces through which individuals could purchase subsidized insurance coverage. However, the effect of these Marketplaces on surgical patients' healthcare spending remains largely unknown.METHODS: We analyzed a nationally representative sample of adults aged 19-64 who underwent surgery in 2010-2017, using the Medical Expenditure Panel Survey. Low-income patients eligible for cost-sharing and premium subsidies in the Marketplaces [income 139%-250% federal poverty level (FPL)] and middle-income patients eligible only for premium subsidies (251%-400% FPL) were compared to high-income controls ineligible for subsidies (>400% FPL) using a quasi-experimental difference-in-differences approach. We evaluated 3 main outcomes: (1) out-of-pocket spending, (2) premium contributions, and (3) likelihood of experiencing catastrophic expenditures, defined as out-of-pocket plus premium spending exceeding 19.5% of family income.RESULTS: Our sample included 5450 patients undergoing surgery, representing approximately 69 million US adults. Among low-income patients, Marketplace implementation was associated with $601 lower [95% confidence interval (CI): -$1169 to -$33; P = 0.04) out-of-pocket spending; $968 lower (95% CI: -$1652 to -$285; P = 0.006) premium spending; and 34.6% lower probability (absolute change: -8.3 percentage points; 95% CI: -14.9 to -1.7; P = 0.01) of catastrophic expenditures. We found no evidence that health expenditures changed for middle-income surgical patients.CONCLUSIONS: The ACA's insurance Marketplaces were associated with improved financial protection among low-income surgical patients eligible for both cost-sharing and premium subsidies, but not in middle-income patients eligible for only premium subsidies.
View details for DOI 10.1097/SLA.0000000000003823
View details for PubMedID 32221119
Association of the US Affordable Care Act With Out-of-Pocket Spending and Catastrophic Health Expenditures Among Adult Patients With Traumatic Injury.
JAMA network open
2020; 3 (2): e200157
Trauma is an expensive and unpredictable source of out-of-pocket spending for American families. The Patient Protection and Affordable Care Act (ACA) sought to improve financial protection by expanding health insurance coverage, but its association with health care spending for patients with traumatic injury remains largely unknown.To evaluate the association of ACA implementation with out-of-pocket spending, premiums, and catastrophic health expenditures (CHE) among adult patients with traumatic injury.Data from a nationally representative sample of US adults aged 19 to 64 years who had a hospital stay or emergency department visit for a traumatic injury from January 2010 to December 2017 were analyzed using the Medical Expenditure Panel Survey. Multivariable generalized linear models were used to evaluate changes in spending after ACA implementation. Additionally, 4 income subgroups were evaluated based on ACA thresholds for program eligibility: lowest-income patients (earning 138% or less of the federal poverty level [FPL]), low-income patients (earning 139% to 250% of the FPL), middle-income patients (earning 251% to 400% of the FPL), and high-income patients (earning more than 400% of the FPL). Data were analyzed from February to December 2019.Implementation of the ACA, beginning January 1, 2014.Out-of-pocket spending, premium spending, out-of-pocket plus premium spending, and likelihood of experiencing CHE, defined as out-of-pocket plus premium spending exceeding 19.5% of family income.Of the 6288 included patients, 2995 (weighted percentage, 51.3%) were male, and the mean (SD) age was 41.4 (12.8) years. Implementation of the ACA was associated with 31% lower odds of CHE (adjusted odds ratio, 0.69; 95% CI, 0.54 to 0.87; P = .002). Changes were greatest in lowest-income patients, who experienced 30% lower out-of-pocket spending (adjusted percentage change, -30.4%; 95% CI, -46.6% to -9.4%; P = .01), 26% lower out-of-pocket plus premium spending (adjusted percentage change, -26.3%; 95% CI, -41.0% to -8.1%; P = .01), and 39% lower odds of CHE (adjusted odds ratio, 0.61; 95% CI, 0.44 to 0.84; P = .002). Low-income patients experienced decreased out-of-pocket spending and out-of-pocket plus premium spending but no changes in CHE, while middle-income and high-income patients experienced no significant changes in any spending outcome. In the post-ACA period, 1 in 11 of all patients with traumatic injury and 1 in 5 with the lowest incomes continued to experience CHE each year.Implementation of the ACA was associated with improved financial protection for US adults with traumatic injury, especially lowest-income individuals targeted by the law's Medicaid expansions. Despite these gains, injured patients remain at risk of financial strain.
View details for DOI 10.1001/jamanetworkopen.2020.0157
View details for PubMedID 32108892
Clinical Effectiveness and Resource Utilization of Surgery vs Endovascular Therapy for Chronic Limb Threatening Ischemia.
Annals of vascular surgery
The clinical effectiveness of surgical versus endovascular therapy for chronic limb threatening ischemia continues to be debated, and the resources required for each therapy are unclear.Systematic review of randomized controlled trials and observational studies comparing surgery with endovascular therapy for chronic limb threatening ischemia, which reported clinical effectiveness and resource utilization. Short- and long-term clinical outcomes were examined.The search yielded 4231 titles, of which 17 publications met our inclusion criteria. Five publications were all from one randomized controlled trial and 12 publications were observational studies. In the randomized controlled trial, the surgical approach had greater resource use in the first year (total hospital days across all admissions for surgery vs. angioplasty: 46.14 ± 53.87 vs. 36.35 ± 51.39, p<0.001; also true for days in high-dependency and intensive-therapy units), but differences were not statistically significant in subsequent years. All-cause mortality presented a nonsignificant difference favoring angioplasty in the first two years (adjusted hazard ratio [aHR] 1.27; 95% confidence interval [CI] 0.75, 2.15), but after two years it favored surgical treatment (aHR 0.34; 95% CI 0.17, 0.71). The observational studies reported short-term effectiveness and resource utilization favoring endovascular therapy, but most differences were not statistically significant. Longer-term outcomes were more mixed; in particular, mortality outcomes generally favored surgery, although concluding cause-and-effect is not possible as endovascularly-treated patients tended to be older and may have had a shorter life expectancy regardless of therapy.The clinical effectiveness and resource utilization of surgery compared to endovascular therapy for chronic limb threatening ischemia is not known with certainty and will not be known until ongoing trials report results. It is likely that findings will vary by the time horizon, where initial outcomes and utilization tend to favor endovascular interventions, but longer-term outcomes favor surgical revascularization.
View details for DOI 10.1016/j.avsg.2020.04.043
View details for PubMedID 32439522
Injuries Associated With Standing Electric Scooter Use.
JAMA network open
2019; 2 (1): e187381
Importance: Since September 2017, standing electric scooters have proliferated rapidly as an inexpensive, easy mode of transportation. Although there are regulations for safe riding established by both electric scooter companies and local governments, public common use practices and the incidence and types of injuries associated with these standing electric scooters are unknown.Objective: To characterize injuries associated with standing electric scooter use, the clinical outcomes of injured patients, and common use practices in the first US metropolitan area to experience adoption of this technology.Design, Setting, and Participants: This study of a case series used retrospective cohort medical record review of all patients presenting with injuries associated with standing electric scooter use between September 1, 2017, and August 31, 2018, at 2 urban emergency departments associated with an academic medical center in Southern California. All electric scooter riders at selected public intersections in the community surrounding the 2 hospitals were also observed during a 7-hour observation period in September 2018.Main Outcomes and Measures: Incidence and characteristics of injuries and observation of riders' common use practices.Results: Two hundred forty-nine patients (145 [58.2%] male; mean [SD] age, 33.7 [15.3] years) presented to the emergency department with injuries associated with standing electric scooter use during the study period. Two hundred twenty-eight (91.6%) were injured as riders and 21 (8.4%) as nonriders. Twenty-seven patients were younger than 18 years (10.8%). Ten riders (4.4%) were documented as having worn a helmet, and 12 patients (4.8%) had either a blood alcohol level greater than 0.05% or were perceived to be intoxicated by a physician. Frequent injuries included fractures (79 [31.7%]), head injury (100 [40.2%]), and contusions, sprains, and lacerations without fracture or head injury (69 [27.7%]). The majority of patients (234 [94.0%]) were discharged home from the emergency department; of the 15 admitted patients, 2 had severe injuries and were admitted to the intensive care unit. Among 193 observed electric scooter riders in the local community in September 2018, 182 (94.3%) were not wearing a helmet.Conclusions and Relevance: Injuries associated with standing electric scooter use are a new phenomenon and vary in severity. In this study, helmet use was low and a significant subset of injuries occurred in patients younger than 18 years, the minimum age permitted by private scooter company regulations. These findings may inform public policy regarding standing electric scooter use.
View details for PubMedID 30681711
Provision of surgical care in Ethiopia: Challenges and solutions
GLOBAL PUBLIC HEALTH
2018; 13 (11): 1691–1701
With the lowest measured rate of surgery in the world, Ethiopia is faced with a number of challenges in providing surgical care. The aim of this study was to elucidate challenges in providing safe surgical care in Ethiopia, and solutions providers have created to overcome them. Semi-structured interviews were conducted with 10 practicing surgeons in Ethiopia. Following de-identification and immersion into field notes, topical coding was completed with an existing coding manual. Codes were adapted and expanded as necessary, and the primary data analyst confirmed reproducibility with a secondary analyst. Qualitative analysis revealed topics in access to care, in-hospital care delivery, and health policy. Patient financial constraints were identified as a challenge to accessing care. Surgeons were overwhelmed by patient volume and frustrated by lack of material resources and equipment. Numerous surgeons commented on the inadequacy of training and felt that medical education is not a government priority. They reported an insufficient number of anaesthesiologists, nurses, and support staff. Perceived inadequate financial compensation and high workload led to low morale among surgeons. Our study describes specific challenges surgeons encounter in Ethiopia and demonstrates the need for prioritisation of surgical care in the Ethiopian health agenda.LCoGS: The Lancet Commission on Global Surgery; LMIC: low- and middle-income country.
View details for PubMedID 29448900
Brief surgical procedure code lists for outcomes measurement and quality improvement in resource-limited settings
2017; 162 (5): 1163–76
The lack of a classification system for surgical procedures in resource-limited settings hinders outcomes measurement and reporting. Existing procedure coding systems are prohibitively large and expensive to implement. We describe the creation and prospective validation of 3 brief procedure code lists applicable in low-resource settings, based on analysis of surgical procedures performed at Mbarara Regional Referral Hospital, Uganda's second largest public hospital.We reviewed operating room logbooks to identify all surgical operations performed at Mbarara Regional Referral Hospital during 2014. Based on the documented indication for surgery and procedure(s) performed, we assigned each operation up to 4 procedure codes from the International Classification of Diseases, 9th Revision, Clinical Modification. Coding of procedures was performed by 2 investigators, and a random 20% of procedures were coded by both investigators. These codes were aggregated to generate procedure code lists.During 2014, 6,464 surgical procedures were performed at Mbarara Regional Referral Hospital, to which we assigned 435 unique procedure codes. Substantial inter-rater reliability was achieved (κ = 0.7037). The 111 most common procedure codes accounted for 90% of all codes assigned, 180 accounted for 95%, and 278 accounted for 98%. We considered these sets of codes as 3 procedure code lists. In a prospective validation, we found that these lists described 83.2%, 89.2%, and 92.6% of surgical procedures performed at Mbarara Regional Referral Hospital during August to September of 2015, respectively.Empirically generated brief procedure code lists based on International Classification of Diseases, 9th Revision, Clinical Modification can be used to classify almost all surgical procedures performed at a Ugandan referral hospital. Such a standardized procedure coding system may enable better surgical data collection for administration, research, and quality improvement in resource-limited settings.
View details for PubMedID 28864101
The How Project: understanding contextual challenges to global surgical care provision in low-resource settings.
BMJ global health
2016; 1 (4)
5 billion people around the world do not have access to safe, affordable, timely surgical care. This series of qualitative interviews was launched by The Lancet Commission on Global Surgery (LCoGS) with the aim of understanding the contextual challenges-the specific circumstances-faced by surgical care providers in low-resource settings who care for impoverished patients, and how those providers overcome these challenges.From January 2014 to February 2015, 20 LCoGS collaborators conducted semistructured interviews with 148 surgical providers in low-resource settings in 21 countries. Stratified purposive sampling was used to include both rural and urban providers, and reputational case selection identified individuals. Interviewers were trained with an implementation manual. Following immersion into de-identified texts from completed interviews, topical coding and further analysis of coded texts was completed by an independent analyst with periodic validation from a second analyst.Providers described substantial financial, geographic and cultural barriers to patient access. Rural surgical teams reported a lack of a trained workforce and insufficient infrastructure, equipment, supplies and banked blood. Urban providers face overcrowding, exacerbated by minimal clinical and administrative support, and limited interhospital care coordination. Many providers across contexts identified national health policies that do not reflect the realities of resource-poor settings. Some findings were region-specific, such as weak patient-provider relationships and unreliable supply chains. In all settings, surgical teams have created workarounds to deliver care despite the challenges.While some differences exist between countries, the barriers to safe surgery and anaesthesia are overall consistent and resource-dependent. Efforts to advance and expand global surgery must address these commonalities, while local policymakers can tailor responses to key contextual differences.
View details for DOI 10.1136/bmjgh-2016-000075
View details for PubMedID 28588976
View details for PubMedCentralID PMC5321373
A qualitative study exploring contextual challenges to surgical care provision in 21 LMICs.
2015; 385: S15-?
Billions of people worldwide are without access to safe, affordable, and timely surgical care. The Lancet Commission on Global Surgery (LCoGS) conducted a qualitative study to understand the contextual challenges to surgical care provision in low-income and middle-income countries (LMICs), and how providers overcome them.A semi-structured interview was administered to 143 care providers in 21 LMICs using stratified purposive sampling to include both urban and rural areas and reputational case selection to identify individual providers. Interviews were conducted in Argentina (n=5), Botswana (3), Brazil (10), Cape Verde (4), China (14), Colombia (4), Ecuador (6), Ethiopia (10), India (15), Indonesia (1), Mexico (9), Mongolia (4), Namibia (2), Pakistan (13), Peru (5), Philippines (1), Sierra Leone (11), Tanzania (5), Thailand (2), Uganda (9), and Zimbabwe (15). Local collaborators of LCoGS conducted interviews using a standardised implementation manual and interview guide. Questions revolved around challenges or barriers in the area of access to care for patients; challenges or barriers in the area of in-hospital care for patients; and challenges or barriers in the area of governance or health policy. De-identified interviews were coded and interpreted by an independent analyst.Providers across continent and context noted significant geographical, financial, and educational barriers to access. Surgical care provision in the rural hospital setting was hindered by a paucity of trained workforce, and inadequacies in basic infrastructure, equipment, supplies, and access to banked blood. In urban areas, providers face high patient volumes combined with staff shortages, minimal administrative support, and poor interhospital care coordination. At a policy level, providers identified regulations that were inconsistent with the realities of low-resource care provision (eg, a requirement to provide 'free' care to certain populations but without any guarantee for funding). Regional variation did exist on some matters, particularly related to prevalence of patient-provider mistrust and supply chain failures. Everywhere, providers have created innovative workarounds to overcome some of these barriers, such as clever financing mechanisms for planned surgery (eg, raising donated farm animals for cash in Zimbabwe, Ethiopia, and India), provision in scheduling and accommodations to facilitate patients from afar, reduction of cost and waste through re-sterilisation of disposable supplies, and locally sourcing consumables (eg, hand cleaning solution made of alcohol from the local distillery in India).Although some variation exists between countries, the challenges to surgical care provision are largely consistent and based on local resource availability; underfunded rural hospitals faced similar challenges worldwide. Global efforts to scale-up surgical services can focus on these commonalities (eg, investments in infrastructure, workforce), while local governments can tailor solutions to key contextual differences (eg, community-based outreach, supply chains, professional management, and interhospital coordination).None.
View details for DOI 10.1016/S0140-6736(15)60810-8
View details for PubMedID 26313061
View details for PubMedCentralID PMC4803468
Geospatial mapping to estimate timely access to surgical care in nine low-income and middle-income countries.
2015; 385: S16-?
The Lancet Commission on Global Surgery calls for universal access to safe, affordable, and timely surgical care. Two requisite components of timely access are (1) the ability to reach a surgical provider in a given timeframe, and (2) the ability to receive appropriately prompt care from that provider. We chose a threshold of 2 h in view of its relevance in time-to-death in post-partum haemorrhage. Here, we use geospatial mapping to enumerate the percentage of a nation's population living within 2 h of a surgeon and the surgeon-to-population ratio for each provider.Geospatial mapping was used to identify the population living within a 2-h driving distance (access zone) of a health-care facility staffed by a surgeon. Surgeon locations were extracted from Ministries of Health, professional society databases, and published literature for countries which had available data. Data were reviewed by individuals knowledgeable of in-country distribution. Spatial distribution of providers was mapped with Google Maps engine. Access zones were constructed around every provider through estimation of driving times in Google Maps. The number of people living within zones was estimated with the Socioeconomic Data and Applications Center Population Estimation Service. Surgeon-to-population ratios were constructed for every individual access zone and averaged to report a single ratio.Results (% country's population living within an access zone; average surgeon:population ratio within all access zones) are reported for nine countries with available data: Somaliland (16·9%; 1:118 306), Botswana (31·0%; 1:64 635), Ethiopia (39·6%; 1:229 696), Rwanda (41·3%; 1:158 484), Namibia (43·4%; 1:69 385), Zimbabwe (54%; 1:148 292), Mongolia (55·5%; 1:10 500), Sierra Leone (70·3%; 1:106 742), and Pakistan (84·4%, 1:139 299). Surgeon-to-population ratios vary substantially even within countries; in Sierra Leone, urban access zones have a ratio of 1:45 058 and rural access zones have a ratio of 1:467 929.Surgical access is poor in many low-income and middle-income countries, even when using a narrow definition of surgical access consisting only of timeliness. Living outside of an access zone makes timely access to surgical care highly unlikely, and in view of low surgeon-to-population ratios and poor prehospital transport, even living within a 2-h access zone might not confer 2-h access. Investments in infrastructure and training must be prioritised to address widespread disparity in access to timely surgery.None.
View details for DOI 10.1016/S0140-6736(15)60811-X
View details for PubMedID 26313062
Hepatic Hydatid Cyst: A Rare Cause of Recurrent Pancreatitis
JOURNAL OF GASTROINTESTINAL SURGERY
2014; 18 (11): 2057-2059
A case of pancreatitis secondary to a hepatic hydatid cyst is illustrated together with its preoperative imaging and intraoperative appearance. Cystobiliary communication is a common complication of large hydatid cysts, and episodes of recurrent pancreatitis resulting from passage of cyst contents down the biliary tract are rarely described. The clinical manifestations, diagnostic workup, and surgical management options of echinococcal-related pancreatitis are discussed, and a review of the literature is provided.
View details for DOI 10.1007/s11605-014-2630-1
View details for Web of Science ID 000343919700022
View details for PubMedID 25149853
California Emergency Department Closures Are Associated With Increased Inpatient Mortality At Nearby Hospitals
2014; 33 (8): 1323-1329
Between 1996 and 2009 the annual number of emergency department (ED) visits in the United States increased by 51 percent while the number of EDs nationwide decreased by 6 percent, which placed unprecedented strain on the nation's EDs. To investigate the effects of an ED's closing on surrounding communities, we identified all ED closures in California during the period 1999-2010 and examined their association with inpatient mortality rates at nearby hospitals. We found that one-quarter of hospital admissions in this period occurred near an ED closure and that these admissions had 5 percent higher odds of inpatient mortality than admissions not occurring near a closure. This association persisted whether we considered ED closures as affecting all future nearby admissions or only those occurring in the subsequent two years. These results suggest that ED closures have ripple effects on patient outcomes that should be considered when health systems and policy makers decide how to regulate ED closures.
View details for DOI 10.1377/hlthaff.2013.1203
View details for Web of Science ID 000340471700004
View details for PubMedID 25092832
Indications, Hospital Course, and Complexity of Patients Undergoing Tracheostomy at a Tertiary Care Pediatric Hospital
OTOLARYNGOLOGY-HEAD AND NECK SURGERY
2014; 151 (2): 232-239
The purpose of this study was to review inpatients undergoing tracheostomies at a tertiary care pediatric hospital in a 24-month period and to identify the indications, comorbidities, hospital course, patient complexity, and predischarge planning for tracheostomy care. The goal was to analyze these factors to highlight potential areas for improvement.Case series with chart review.Tertiary care pediatric hospital.Ninety-five inpatients at Boston Children's Hospital requiring a primary or revision tracheostomy during the 24-month period encompassing 2010 to 2011.Inpatients undergoing tracheostomy during the study period were identified using 2 different databases: the Boston Children's Hospital Department of Otolaryngology and Communication Enhancement database and institution-specific information from the Child Health Corporation of America's Pediatric Health Information System (PHIS). We extracted the specified metrics from the inpatient charts.Patients undergoing tracheostomy are complex, with an average of 3.4 comorbidities and 13.6 services involved in their care. The tracheostomy was mentioned in 97.9% of physician and 69.5% of nurse discharge notes, and 42.5% of physician discharge notes contained a plan or appointment for follow-up. Of the patients, 33.7% were discharged home (27.3% of the nonanatomic group and 52.4% of the anatomic group). Overall, 8.4% of tracheostomy patients died before discharge.The complexity of pediatric tracheostomy patients presents challenges and opportunities for optimizing quality of care for these children. Future directions include the introduction and assessment of multidisciplinary tracheostomy care teams, tracheostomy nurse specialists, and tracheostomy care plans in the pediatric setting.
View details for DOI 10.1177/0194599814531731
View details for Web of Science ID 000340453300008
View details for PubMedID 24788698
Decoupling catalytic activity from biological function of the ATPase that powers lipopolysaccharide transport
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2014; 111 (13): 4982-4987
The cell surface of Gram-negative bacteria contains lipopolysaccharides (LPS), which provide a barrier against the entry of many antibiotics. LPS assembly involves a multiprotein LPS transport (Lpt) complex that spans from the cytoplasm to the outer membrane. In this complex, an unusual ATP-binding cassette transporter is thought to power the extraction of LPS from the outer leaflet of the cytoplasmic membrane and its transport across the cell envelope. We introduce changes into the nucleotide-binding domain, LptB, that inactivate transporter function in vivo. We characterize these residues using biochemical experiments combined with high-resolution crystal structures of LptB pre- and post-ATP hydrolysis and suggest a role for an active site residue in phosphate exit. We also identify a conserved residue that is not required for ATPase activity but is essential for interaction with the transmembrane components. Our studies establish the essentiality of ATP hydrolysis by LptB to power LPS transport in cells and suggest strategies to inhibit transporter function away from the LptB active site.
View details for DOI 10.1073/pnas.1323516111
View details for Web of Science ID 000333579700069
View details for PubMedID 24639492